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Why doesn't a basic side chain (R group) of an amino acid form a peptide bond in protein biosynthesis?

Why doesn't a basic side chain (R group) of an amino acid form a peptide bond in protein biosynthesis?



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Why doesn't a basic side chain (R group) of an amino acid form a peptide bond in protein biosynthesis?

Consider lysine, for example, why can't its side-chain amino group, -(CH2)4-NH2, form a peptide bond with the carboxyl group of the other amino acid? Is it due to orientation alone are their other properties involved?


Asparagine

Asparagine (symbol Asn or N [2] ), is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH +
3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO − form under biological conditions), and a side chain carboxamide, classifying it as a polar (at physiological pH), aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it. It is encoded by the codons AAU and AAC.

  • 70-47-3 Y
  • CHEBI:17196 Y
  • ChEMBL58832 Y
  • 6031 Y
  • DB03943 Y
  • C00152 Y
  • 5Z33R5TKO7 Y
InChI=1S/C4H8N2O3/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H2,6,7)(H,8,9)/t2-/m0/s1 Y Key: DCXYFEDJOCDNAF-REOHCLBHSA-N Y

A reaction between asparagine and reducing sugars or other source of carbonyls produces acrylamide in food when heated to sufficient temperature. These products occur in baked goods such as French fries, potato chips, and toasted bread.


The nonpolar molecules we'll be talking about are hydrophobic amino acids, meaning "water fearing" because they don't mix with water molecules. You know how oil and water don't mix? That's because oil is hydrophobic.

The opposite of a nonpolar molecule is, as you might guess, polar. Polar molecules are hydrophilic, meaning "water loving." If you'd like to visualize: polar molecules are like puppy dogs who love water so much that they'll go barreling straight into muddy or smelly water after a tennis ball, with no hesitation at all. That would make nonpolar molecules like cats, better known for avoiding water, no thank you, and cleaning themselves without it.

Molecules are classified this way based on the charges on the atoms bonded together to form the molecule. If you remember your first taste of high school chemistry, you may remember that atoms have a nucleus of neutral neutrons and positive protons in the middle, and negative electrons swirling all around. Protons have a positive charge that draws electrons to it, like how opposites attract.

When two atoms bond together, they share electrons. Two atoms of the same element have equal positivity, so don't have the power to steal electrons from the other. These molecules are nonpolar because they have no resulting charge. When atoms of two different elements connect together, invariably one of them will have the higher charge and attract the most electrons to its end of the joint molecule. That means the molecule is polar, or charged, and that charge will then be identified as either a positive or negative charge.


3.2.1. Proteins Have Unique Amino Acid Sequences That Are Specified by Genes

In 1953, Frederick Sanger determined the amino acid sequence of insulin, a protein hormone (Figure 3.22). This work is a landmark in biochemistry because it showed for the first time that a protein has a precisely defined amino acid sequence. Moreover, it demonstrated that insulin consists only of l amino acids linked by peptide bonds between α-amino and α-carboxyl groups. This accomplishment stimulated other scientists to carry out sequence studies of a wide variety of proteins. Indeed, the complete amino acid sequences of more than 100,000 proteins are now known. The striking fact is that each protein has a unique, precisely defined amino acid sequence. The amino acid sequence of a protein is often referred to as its primary structure.

Figure 3.22

Amino Acid Sequence of Bovine Insulin.

A series of incisive studies in the late 1950s and early 1960s revealed that the amino acid sequences of proteins are genetically determined. The sequence of nucleotides in DNA, the molecule of heredity, specifies a complementary sequence of nucleotides in RNA, which in turn specifies the amino acid sequence of a protein. In particular, each of the 20 amino acids of the repertoire is encoded by one or more specific sequences of three nucleotides (Section 5.5).

Knowing amino acid sequences is important for several reasons. First, knowledge of the sequence of a protein is usually essential to elucidating its mechanism of action (e.g., the catalytic mechanism of an enzyme). Moreover, proteins with novel properties can be generated by varying the sequence of known proteins. Second, amino acid sequences determine the three-dimensional structures of proteins. Amino acid sequence is the link between the genetic message in DNA and the three-dimensional structure that performs a protein's biological function. Analyses of relations between amino acid sequences and three-dimensional structures of proteins are uncovering the rules that govern the folding of polypeptide chains. Third, sequence determination is a component of molecular pathology, a rapidly growing area of medicine. Alterations in amino acid sequence can produce abnormal function and disease. Severe and sometimes fatal diseases, such as sickle-cell anemia and cystic fibrosis, can result from a change in a single amino acid within a protein. Fourth, the sequence of a protein reveals much about its evolutionary history (see Chapter 7). Proteins resemble one another in amino acid sequence only if they have a common ancestor. Consequently, molecular events in evolution can be traced from amino acid sequences molecular paleontology is a flourishing area of research.


Why doesn't a basic side chain (R group) of an amino acid form a peptide bond in protein biosynthesis? - Biology

INTRODUCING AMINO ACIDS

This page explains what amino acids are, concentrating on the 2-amino acids that are biologically important. It looks in some detail at their simple physical properties such as solubility and melting points.

Amino acids are exactly what they say they are! They are compounds containing an amino group, -NH2, and a carboxylic acid group, -COOH.

The biologically important amino acids have the amino group attached to the carbon atom next door to the -COOH group. They are known as 2-amino acids. They are also known (slightly confusingly) as alpha-amino acids. These are the ones we will concentrate on.

The two simplest of these amino acids are 2-aminoethanoic acid and 2-aminopropanoic acid.

Because of the biological importance of molecules like these, they are normally known by their traditional biochemical names.

2-aminoethanoic acid, for example, is usually called glycine, and 2-aminopropanoic acid is usually known as alanine.

The general formula for a 2-amino acid is:

. . . where "R" can be quite a complicated group containing other active groups like -OH, -SH, other amine or carboxylic acid groups, and so on. It is definitely NOT necessarily a simple hydrocarbon group!

Note: For complete accuracy, one of the 20 biologically important amino acids (proline) has a slightly different structure. The "R" group is bent into a circle which attaches itself to the nitrogen again in place of one of the hydrogens. This complication doesn't actually make much difference to the chemistry of the compound - the nitrogen still behaves in the same way as it does in the other amino acids. This isn't something you need to worry about for chemistry purposes at this introductory level.

The amino acids are crystalline solids with surprisingly high melting points. It is difficult to pin the melting points down exactly because the amino acids tend to decompose before they melt. Decomposition and melting tend to be in the 200 - 300°C range.

For the size of the molecules, this is very high. Something unusual must be happening.

If you look again at the general structure of an amino acid, you will see that it has both a basic amine group and an acidic carboxylic acid group.

There is an internal transfer of a hydrogen ion from the -COOH group to the -NH2 group to leave an ion with both a negative charge and a positive charge.

This is called a zwitterion.

A zwitterion is a compound with no overall electrical charge, but which contains separate parts which are positively and negatively charged.

This is the form that amino acids exist in even in the solid state. Instead of the weaker hydrogen bonds and other intermolecular forces that you might have expected, you actually have much stronger ionic attractions between one ion and its neighbours.

These ionic attractions take more energy to break and so the amino acids have high melting points for the size of the molecules.

Amino acids are generally soluble in water and insoluble in non-polar organic solvents such as hydrocarbons.

This again reflects the presence of the zwitterions. In water, the ionic attractions between the ions in the solid amino acid are replaced by strong attractions between polar water molecules and the zwitterions. This is much the same as any other ionic substance dissolving in water.

The extent of the solubility in water varies depending on the size and nature of the "R" group.

Note: At this point I would normally try to relate the actual values for solubility of the various amino acids to their structures. Unfortunately, from the solubility values that I have got (and I'm not convinced they are necessarily right), I can't find any obvious patterns - in fact, there are some very strange cases indeed.

The lack of solubility in non-polar organic solvents such as hydrocarbons is because of the lack of attraction between the solvent molecules and the zwitterions. Without strong attractions between solvent and amino acid, there won't be enough energy released to pull the ionic lattice apart.

If you look yet again at the general formula for an amino acid, you will see that (apart from glycine, 2-aminoethanoic acid) the carbon at the centre of the structure has four different groups attached. In glycine, the "R" group is another hydrogen atom.

This is equally true if you draw the structure of the zwitterion instead of this simpler structure.

Because of these four different groups attached to the same carbon atom, amino acids (apart from glycine) are chiral.

Important: If you don't know exactly what that means, follow this link to the page about optical isomerism. You will find the optical activity of amino acids discussed at the bottom of that page, but read the whole page to be sure that you understand what is going on.

Use the BACK button on your browser to return to this page.

The lack of a plane of symmetry means that there will be two stereoisomers of an amino acid (apart from glycine) - one the non-superimposable mirror image of the other.

For a general 2-amino acid, the isomers are:

Note: If you don't know what the various bond symbols mean, you shouldn't have got this far! Follow the link mentioned above to the page about optical isomerism. Read that page and follow the further link on that page to drawing organic molecules.

Use the BACK button on your browser to return to this page.

All the naturally occurring amino acids have the right-hand structure in this diagram. This is known as the "L-" configuration. The other one is known as the "D-" configuration.

You almost certainly don't need to know this for UK A level chemistry purposes, but if you are interested, you can recognise the L- configuration by imagining that you are looking down from above on the right-hand structure in the last diagram - in other words, with the hydrogen atom closest to you. If you read around the other groups in a clockwise direction, you get the word CORN.

Warning: There are various other ways of working this out also based on the word CORN, but by looking at the molecule from a different viewpoint which could mean that CORN has to be applied anti-clockwise rather than clockwise for the L- form.

If you have already learnt a different rule, then stick to it. If you are an A level (or equivalent) chemistry student, find out what (if anything) your examiners expect, and learn that. If you don't need to know about it, forget it!

You can't tell by looking at a structure whether that isomer will rotate the plane of polarisation of plane polarised light clockwise or anticlockwise. All the naturally occurring amino acids have the same L- configuration, but they include examples which rotate the plane clockwise (+) and those which do the opposite (-).

It is quite common for natural systems to only work with one of the optical isomers (enantiomers) of an optically active substance like the amino acids. It isn't too difficult to see why that might be. Because the molecules have different spatial arrangements of their various groups, only one of them is likely to fit properly into the active sites on the enzymes they work with.

Questions to test your understanding

If this is the first set of questions you have done, please read the introductory page before you start. You will need to use the BACK BUTTON on your browser to come back here afterwards.


What are aromatic amino acids?

Aromatic amino acids are amino acids that have an aromatic ring in the side-chain.

Amino acids are biologically important organic compounds that contain amine (-NH2) and carboxylic acid (-COOH) functional groups, with a side-chain (-R) specific to each amino acid.

The general formula of an amino acid is NH₂CHRCOOH.

Four of the 21 standard amino acids have aromatic rings in their side-chains.

The diagram below shows the structures of phenylalanine, tyrosine, tryptophan, and histidine.

Some less common amino acids are

Thyroxine is derived from tyrosine. It is the ultimate metabolism regulator. It influences carbohydrate metabolism, protein synthesis and breakdown, and cardiovascular, renal, and brain function.

5-Hydroxytrytophan

5-Hydroxytryptophan is an intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan.


4. Non protein coding RNAs (a.k.a non-coding RNAs or ncRNAs)

The expression of proteins is determined by genomic information, and their presence supports the function of cell life. Parts of an organism’s genome are transcribed in an orderly tissue- and developmental phase- specific manner into RNA transcripts that are destined to effect the eventual production of proteins.

Until fairly recently, it was believed that the molecules that are important for the function of a cell are those described by the “Central Dogma” of biology, namely messenger RNAs and proteins. Things began to change with the discovery of microRNAs more than 20 years ago in plants 16 and animals 17,18 . Subsequent research efforts have demonstrated that large parts of an organism’s genome will be transcribed at one time point or another into RNA, but will not be translated into an amino acid sequence. These RNA transcripts have been referred to as ncRNAs and there is increased appreciation that many of them are indeed functional and affect key cellular processes.

There are many recognizable classes of ncRNAs, each having a distinct functionality. These include: transfer RNAs (tRNAs) 19 ribosomal RNAs (rRNAs) 20 the above-mentioned miRNAs 17,18 small nucleolar RNAs (snoRNAs) 21,22 piwi-interacting (piRNAs) 23󈞅 transcription initiation RNAs (tiRNAs) 26 human microRNA-offset (moRNAs) 27 sno-derived RNAs (sdRNAs) 28 long intergenic ncRNAs (lincRNAs) 29 etc. The full extent of distinct classes of ncRNAs that are encoded within the human genome is currently unknown but are believed to be numerous.

  • Short non-coding RNAs: At least three classes of small RNAs are encoded in our genome, based on their biogenesis mechanism and the type of Ago protein that they are associated with miRNAs, endogenous siRNAs and piRNAs. It should be noted, however, that the recent discoveries of numerous non‐canonical small RNAs have somewhat blurred the boundaries between the classes.
  • MicroRNAs (miRNAs): MicroRNAs (miRNAs) comprise a large family of naturally occurring, endogenous, single-stranded

22-nucleotide-long RNAs. MiRNAs function as key post-transcriptional regulators of gene expression by base-pairing with their target mRNAs. Originally believed to effect their impact exclusively through the target mRNAs 3´UTR 30 , they have since been shown to have extensive coding region targets as well 12,31 . More than one thousand miRNAs are currently known for the human genome, and each of them has the ability to down regulate the expression of possibly thousands of protein coding genes 32 . In mammals, miRNAs are predicted to control more than

Canonical Pathway

  • In the canonical pathway, transcription of the primary miRNA precursor (pri-miRNA) is carried out by RNA polymerase II. The pri-miRNA is processed into a precursor miRNA (pre-miRNA) by the “microprocessor complex” which comprises Drosha, a member of the RNase III family of endonucleases, and DGCR8, a double-stranded-RNA-binding protein. Pre-miRNAs are generaly 60-70-nucleotides in length, have a two-nucleotide overhang at the 3′ end and a 5′ phosphate group, and fold into a characteristic hairpin-like structure. Exportin-5 recognizes the two-nucleotide 3´-overhang, characteristic of RNase III-mediated cleavage, and shuttles the pre-miRNA through the nuclear pore into the cytoplasm, where it is further processed by Dicer, another endonuclease. Dicer pairs with TRBP and PACT, both double-stranded-RNA-binding proteins, and cleaves the pre-miRNA to form a transient

Alternative pathways (non-canonical)

  • Drosha independent pathways: As mentioned above, most miRNAs either originate form their own transcription units or derive from the exons or introns of other genes 33 and require both Drosha and Dicer for cleavage in their maturation. It was recently shown however first in Droshophila 33 and later in mammals 34 that short hairpin introns, called mirtrons can be alternative sources of miRNAs. Although there are several differences between mammalian and invertebrate mirtrons, both are Drosha independent. Mirtrons are short introns with hairpin potential that can be spliced and debranched into pre-miRNA mimics and then enter the canonical pathway. Post nuclear export, they can then be cleaved by Dicer and incorporated into RISC 34 .
  • Dicer independent pathways: MiRNA biogenesis independent of Dicer has only been described thus far for miR-451 34 . This miRNA is processed by Drosha but its does not require Dicer. Instead, its pre-miRNA, once loaded into Ago, is cleaved by the Ago catalytic centre to generate an intermediate 3’ end, which is further trimmed. Importantly, the Ago catalytic function for the miR-451 biogenesis was shown in Ago2 homozygous mutants that were found to have loss of miR-451 and died shortly after their birth with anemia 34 .

The biological role of long ncRNAs as a class remains largely elusive. Several specific cases have been shown to be involved in transcriptional gene silencing, and the activation of critical regulators of development and differentiation: these exerted their regulatory roles by interfering with transcription factors or their co-activators, though direct action on DNA duplex, by regulating adjacent protein-coding gene expression, by mediating DNA epigenetic modifications, etc.

4.1 RNA splicing

4.2 RNA reverse transcription

Reverse transcription is the transfer of information from RNA to DNA (the reverse of normal transcription). This is known to occur in the case of retroviruses, such as HIV, as well as in eukaryotes, in the case of retrotransposons and telomere synthesis.

4.3 RNA editing / post-transcriptional modifications

Post-transcriptional modification is a process in cell biology by which, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA (mRNA), which includes splicing and occurs prior to protein synthesis. This process is vital for the correct translation of the genomes of eukaryotes as the human primary RNA transcript that is produced as a result of transcription contains both exons, which are coding sections of the primary RNA transcript and introns, which are the non coding sections of the primary RNA transcript.

Post-trancriptional modifications that lead to a mature mRNA include the (i) addition of a methylated guanine cap to the 5′ end of mRNA and (ii) the addition of a poly-A tail to the other end. The cap and tail protect the mRNA from enzyme degradation and aid its attachment to the ribosome. In addition, (iii) introns (non-coding) sequences are spliced out of the mRNA and exons (coding) sequences are spliced together. The mature mRNA transcript will then undergo translation 64 .


First up are the essential amino acids. These are the nine amino acids that your body cannot create on its own, and that you must obtain by eating various foods. Adults need to eat foods that contain the following eight amino acids: methionine, valine, tryptophan, isoleucine, leucine, lysine, threonine and phenylalanine. Histidine, the ninth amino acid, is only necessary for babies.

Instead of storing up a supply of the essential acids, the body uses them to create new proteins on a regular basis. Therefore, the body needs a continual – ideally daily – supply of these amino acids to stay healthy.


CH103 – Chapter 8: The Major Macromolecules

Within all lifeforms on Earth, from the tiniest bacterium to the giant sperm whale, there are four major classes of organic macromolecules that are always found and are essential to life. These are the carbohydrates, lipids (or fats), proteins, and nucleic acids. All of the major macromolecule classes are similar, in that, they are large polymers that are assembled from small repeating monomer subunits. In Chapter 6, you were introduced to the polymers of life and their building block structures, as shown below in Figure 11.1. Recall that the monomer units for building the nucleic acids, DNA and RNA, are the nucleotide bases, whereas the monomers for proteins are amino acids, for carbohydrates are sugar residues, and for lipids are fatty acids or acetyl groups.

This chapter will focus on an introduction to the structure and function of these macromolecules. You will find that the major macromolecules are held together by the same chemical linkages that you’ve been exploring in Chapters 9 and 10, and rely heavily on dehydration synthesis for their formation, and hydrolysis for their breakdown.

Figure 11.1: The Molecular building blocks of life are made from organic compounds.

Fun Video Tutorial Introducing the Major Macromolecules

11.2 Protein Structure and Function

Amino Acids and Primary Protein Structure

The major building block of proteins are called alpha amino acids. As their name implies they contain a carboxylic acid functional group and an amine functional group. The alpha designation is used to indicate that these two functional groups are separated from one another by one carbon group. In addition to the amine and the carboxylic acid, the alpha carbon is also attached to a hydrogen and one additional group that can vary in size and length. In the diagram below, this group is designated as an R-group. Within living organisms there are 20 amino acids used as protein building blocks. They differ from one another only at the R-group postion. The basic structure of an amino acid is shown below:

Figure 11.2 General Structure of an Alpha Amino Acid

Within cellular systems, proteins are linked together by a complex system of RNA and proteins called the ribosome. Thus, as the amino acids are linked together to form a specific protein, they are placed within a very specific order that is dictated by the genetic information contained within the RNA. This specific ordering of amino acids is known as the protein’s primary sequence. The primary sequence of a protein is linked together using dehydration synthesis that combine the carboxylic acid of the upstream amino acid with the amine functional group of the downstream amino acid to form an amide linkage. Within protein structures, this amide linkage is known as the peptide bond. Subsequent amino acids will be added onto the carboxylic acid terminal of the growing protein. Thus, proteins are always synthesized in a directional manner starting with the amine and ending with the carboxylic acid tail. New amino acids are always added onto the carboxylic acid tail, never onto the amine of the first amino acid in the chain. In addition, because the R-groups can be quite bulky, they usually alternate on either side of the growing protein chain in the trans conformation. The cis conformation is only preferred with one specific amino acid known as proline.

Figure 11.3 Formation of the Peptide Bond. The addition of two amino acids to form a peptide requires dehydration synthesis.

Proteins are very large molecules containing many amino acid residues linked together in very specific order. Proteins range in size from 50 amino acids in length to the largest known protein containing 33,423 amino acids. Macromolecules with fewer than 50 amino acids are known as peptides.


Figure 11.4 Peptides and Proteins are macromolecules built from long chains of amino acids joined together through amide linkages.

The identity and function of a peptide or a protein is determined by the primary sequence of amino acids within its structure. There are a total of 20 alpha amino acids that are commonly incorporated into protein structures (Figure 11.5).

Figure 11.5 Structure of the 20 Alpha Amino Acids used in Protein Synthesis.

Due to the large pool of amino acids that can be incorporated at each position within the protein, there are billions of different possible protein combinations that can be used to create novel protein structures! For example, think about a tripeptide made from this amino acid pool. At each position there are 20 different options that can be incorporated. Thus, the total number of resulting tripeptides possible would be 20 X 20 X 20 or 20 3 , which equals 8,000 different tripeptide options! Now think about how many options there would be for a small peptide containing 40 amino acids. There would be 20 40 options, or a mind boggling 1.09 X 10 52 potential sequence options! Each of these options would vary in the overall protein shape, as the nature of the amino acid side chains helps to determine the interaction of the protein with the other residues in the protein itself and with its surrounding environment. Thus, it is useful to learn a little bit about the general characteristics of the amino acid side chains.

The different amino acid side chains can be grouped into different classes based on their chemical properties (Figure 11.5). For example, some amino acid side chains only contain carbon and hydrogen and are thus, very nonpolar and hydrophobic. Others contain electronegative functional groups with oxygen or nitrogen and can form hydrogen bonds forming more polar interactions. Still others contain carboxylic acid functional groups and can act as acids or they contain amines and can act as bases, forming fully charged molecules. The character of the amino acids throughout the protein help the protein to fold and form its 3-dimentional structure. It is this 3-D shape that is required for the functional activity of the protein (ie. protein shape = protein function). For proteins found inside the watery environments of the cell, hydrophobic amino acids will often be found on the inside of the protein structure, whereas water-loving hydrophilic amino acids will be on the surface where they can hydrogen bond and interact with the water molecules. Proline is unique because it has the only R-group that forms a cyclic structure with the amine functional group in the main chain. This cyclization is what causes proline to adopt the cis conformation rather than the trans conformation within the backbone. This shift is structure will often mean that prolines are positions where bends or directional changes occur within the protein. Methionine is unique, in that it serves as the starting amino acid for almost all of the many thousands of proteins known in nature. Cysteines contain thiol functional groups and thus, can be oxidized with other cysteine residues to form disulfide bonds within the protein structure (Figure 11.6). Disulfide bridges add additional stability to the 3-D structure and are often required for correct protein folding and function (Figure 11.6).

Figure 11.6 Disulfide Bonds. Disulfide bonds are formed between two cysteine residues within a peptide or protein sequence or between different peptide or protein chains. In the example above the two peptide chains that form the hormone insulin are depicted. Disulfide bridges between the two chains are required for the proper function of this hormone to regulate blood glucose levels.

Protein Shape and Function

The primary structure of each protein leads to the unique folding pattern that is characteristic for that specific protein. Recall that this is the linear order of the amino acids as they are linked together in the protein chain (Figure 11.7).

Figure 11.7 Primary protein structure is the linear sequence of amino acids.

(credit: modification of work by National Human Genome Research Institute)

Within each protein small regions may adopt specific folding patterns. These specific motifs or patterns are called secondary structure. Common secondary structural features include alpha helix and beta-pleated sheet (Figure 11.8). Within these structures, intramolecular interactions, especially hydrogen bonding between the backbone amine and carbonyl functional groups are critical to maintain 3-dimensional shape. Every helical turn in an alpha helix has 3.6 amino acid residues. The R groups (the variant groups) of the polypeptide protrude out from the α-helix chain. In the β-pleated sheet, the “pleats” are formed by hydrogen bonding between atoms on the backbone of the polypeptide chain. The R groups are attached to the carbons and extend above and below the folds of the pleat. The pleated segments align parallel or antiparallel to each other, and hydrogen bonds form between the partially positive nitrogen atom in the amino group and the partially negative oxygen atom in the carbonyl group of the peptide backbone. The α-helix and β-pleated sheet structures are found in most proteins and they play an important structural role.

Figure 11.8 Secondary Structural Features in Protein Structure. The alpha helix and beta-pleated sheet are common structural motifs found in most proteins. They are held together by hydrogen bonding between the amine and the carbonyl oxygen within the amino acid backbone.

A Closer Look: Secondary Protein Structure in Silk

There were many trade routes throughout the ancient world. The most highly traveled and culturally significant of these was called the Silk Road. The Silk Road ran from the Chinese city of Chang’an all the way through India and into the Mediterranean and Egypt. The reason that the Silk road was so culturally significant was because of the great distance that it covered. Essentially the entire ancient world was connected by one trade route.

Figure 11. 9 Silkworms

On the route many things were traded, including silk, spices, slaves, ideas, and gun powder. The silk road had an astounding effect on the creation of many societies. It was able to bring economic wealth into areas along the route, and new ideas traveled the distance and influence many things including art. An example of this is Buddhist art that was found in India. The painting has many western influences that can be identified in it, such as realistic musculature of the people being painted. Also, the trade of gun powder to the West helped influence warfare, and in turn shaped the modern world. The real reason the Silk Road was started though was for the product that it takes its name from: Silk.

Figure 11.10 Land route in Red, Sea route in Blue

Silk was prized by the Kings and Queens of both European and Middle Eastern Society. The Silk showed that the rulers had power and wealth because the silk was not easy to come by, and therefore was definitely not cheap. Silk was first developed in China, and is made by harvesting the silk from the cocoons of the mulberry silkworm. The silk itself is called a natural protein fiber because it is composed of a pattern of amino acids in a secondary protein structure. The secondary structure of silk is the beta pleated sheet. The primary structure of silk contains the amino acids of glycine, alanine, serine, in specific repeating pattern. These three amino acids make up 90% of the protein in silk. The last 10% is comprised of the amino acids glutamic acid, valine, and aspartic acid. These amino acids are used as side chains and affect things such as elasticity and strength. they also vary between various species. The beta pleated sheet of silk is connected by hydrogen bonds. The hydrogen bonds in the silk form beta pleated sheets rather than alpha helixes because of where the bonds occur. The hydrogen bonds go from the amide hydrogens on one protein chain to the corresponding carbonyl oxygen across the way on the other protein chain. This is in contrast to the alpha helix because in that structure the bonds go from the amide to the carbonyl oxygen, but they are not adjacent. The carbonyl oxygen is on the amino acid that is four residues before.

Figure 11.11 Parallel and Antiparallel Beta-Pleated Sheets

Silk is a great example of the beta pleated sheet structure. The formation of this secondary structure in the silk protein allows it to have very strong tensile strength. Silk also helped to form one of the greatest trading routes in history, allowing for the exchange of ideas, products and cultures while advancing the societies that were involved. Silk contains both anti-parallel and parallel arrangements of beta sheets. Unlike the α helix, though, the side chains are squeezed rather close together in a pleated-sheet arrangement. In consequence very bulky side chains make the structure unstable. This explains why silk is composed almost entirely of glycine, alanine, and serine, the three amino acids with the smallest side chains. Some species of silk worm produce varying amounts of bulky side chains, but these silks are not as prized as the mulberry silkworm (which has no bulky amino acid side chains) because the silk with bulky side chains is weaker and doesn’t have as much tensile strength.

The complete 3-dimensional shape of the entire protein (or sum of all the secondary structures) is known as the tertiary structure of the protein and is a unique and defining feature for that protein (Figure 11.12). Primarily, the interactions among R groups creates the complex three-dimensional tertiary structure of a protein. The nature of the R groups found in the amino acids involved can counteract the formation of the hydrogen bonds described for standard secondary structures. For example, R groups with like charges are repelled by each other and those with unlike charges are attracted to each other (ionic bonds). When protein folding takes place, the hydrophobic R groups of nonpolar amino acids lay in the interior of the protein, whereas the hydrophilic R groups lay on the outside. The former types of interactions are also known as hydrophobic interactions. Interaction between cysteine side chains forms disulfide linkages in the presence of oxygen, the only covalent bond forming during protein folding.

Figure 11.12 Tertiary Protein Structure. The tertiary structure of proteins is determined by a variety of chemical interactions. These include hydrophobic interactions, ionic bonding, hydrogen bonding and disulfide linkages.

All of these interactions, weak and strong, determine the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it is usually no longer be functional.

In nature, some proteins are formed from several polypeptides, also known as subunits, and the interaction of these subunits forms the quaternary structure. Weak interactions between the subunits help to stabilize the overall structure. For example, insulin (a globular protein) has a combination of hydrogen bonds and disulfide bonds that cause it to be mostly clumped into a ball shape. Insulin starts out as a single polypeptide and loses some internal sequences during cellular processing that form two chains held together by disulfide linkages as shown in figure 11.6. Three of these structures are then grouped further forming an inactive hexamer (Figure 11.13). The hexamer form of insulin is a way for the body to store insulin in a stable and inactive conformation so that it is available for release and reactivation in the monomer form.

Figure 11.13 The Insulin Hormone is a Good Example of Quaternary Structure. Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available.

The four levels of protein structure (primary, secondary, tertiary, and quaternary) are summarized in Figure 11.14.

Figure 11.14 The four levels of protein structure can be observed in these illustrations. (credit: modification of work by National Human Genome Research Institute)

Hydrolysis is the breakdown of the primary protein sequence by the addition of water to reform the individual amino acids monomer units.

Figure 11.15 Hydrolysis of Proteins. In the hydrolysis reaction, water is added across the amide bond incorporating the -OH group with the carbonyl carbon and reforming the carboxylic acid. The hydrogen from the water reforms the amine.

If the protein is subject to changes in temperature, pH, or exposure to chemicals, the protein structure may unfold, losing its shape without breaking down the primary sequence in what is known as denaturation(Figure 11.16). Denaturationis different from hydrolysis, in that the primary strcture of the protein is not affected. Denaturation is often reversible because the primary structure of the polypeptide is conserved in the process if the denaturing agent is removed, allowing the protein to refold and resume its function. Sometimes, however, denaturation is irreversible, leading to a permanent loss of function. One example of irreversible protein denaturation is when an egg is fried. The albumin protein in the liquid egg white is denatured when placed in a hot pan. Note that not all proteins are denatured at high temperatures for instance, bacteria that survive in hot springs have proteins that function at temperatures close to boiling. The stomach is also very acidic, has a low pH, and denatures proteins as part of the digestion process however, the digestive enzymes of the stomach retain their activity under these conditions.

Figure 11.16 Protein Denaturation. Figure (1) depicts the correctly folded intact protein. Step (2) applies heat to the system that is above the threshold of maintaining the intramolecular protein interactions. Step (3) shows the unfolded or denatured protein. Colored regions in the denatured protein correspond to the colored regions of the natively folded protein shown in (1).

Protein folding is critical to its function. It was originally thought that the proteins themselves were responsible for the folding process. Only recently was it found that often they receive assistance in the folding process from protein helpers known as chaperones (or chaperonins) that associate with the target protein during the folding process. They act by preventing aggregation of polypeptides that make up the complete protein structure, and they disassociate from the protein once the target protein is folded.

Proteins are involved in many cellular functions. Proteins can act as enzymes which enhance the rate of chemical reactions. In fact, 99% of enzymatic reactions within a cell are mediated by proteins. Thus, they are integral in the processes of building up or breaking down of cellular components. Proteins can also act as structural scaffolding within the cell, helping to maintain cellular shape. Proteins can also be involved in cellular signaling and communication, as well as the transport of molecules from one location to another. Under extreme circumstances such as starvation, proteins can also be used as an energy source within the cell.