Proteins
4.3 Protein structure
Glycine
Nonpolar Amino Acids
Polar Amino Acids
Alanine Valine Leucine Isoleucine
Phenylalanine Tryptophan Methionine Cysteine Proline
Serine Threonine Tyrosine Asparagine Glutamine
H3N C C O− H
H O
+ H3N C C O−
H
CH3 O
+ H3N C C O−
H O
+
CH H3C CH3
H3N C C O−
H O
+
CH H3C CH3
CH2
H3N C C O−
H O
+
C CH2
CH3 H
CH3
H3N C C O− H
CH2 O
+ H3N C C O−
H
CH2 O
+
N H
H3N C C O− H
CH2 O
+
CH2 S CH3
H3N C C O− H
CH2 O
+
SH
C C O− H
CH2 O HN
H2C CH2
H3N C C O− H
CH2
O
+
C O NH2 H3N C C O−
H
C O
+
H OH H
H3N C C O− H
C O
+
CH3 OH H
H3N C C O− H
CH2
O
+
OH
H3N C C O−
H O
+
CH2
CH2 C O NH2
Figure 4.3 The specific structure of each of the 20 amino acids
H3N C C
Aspartate Glutamate Lysine
Basic Amino Acids Acidic Amino Acids
Arginine Histidine
O− H
CH2
O
+
H3N C C O− H
CH2
O
+
H3N C C O− H
CH2
O
+
H3N C C O− H
CH2
O
+
CH2
H3N C C O−
H O
+
C O O−
CH2
C O O−
CH2
CH2
CH2
NH3
+
CH2
N C NH2
NH2
H
+
CH2 C HN
CH NH CH
+
Figure 4.3 (continued)
N H
H
Amino group
Carboxyl group
Peptide linkage
C terminus N terminus
H H
R
+ −
C O
O H N C C
O O− R
H
H2O
H H
N C C
O O− R
H H C
N H
H
H H
R
+
C O C
Figure 4.4 An example of the peptide bond forming between two neighbouring amino acids
Depending on the number of amino acids present in the peptide chain, we can use prefixes to characterize the number present. For example:
di =two;tri =three;tetra =four;penta=five;
hexa = six;hepta = seven; octa = eight; nona
= nine and deca = ten. The term oligopeptide is used to refer to a peptide chain that consists of 10–20 amino acids. Apolypeptideis the term used to describe a large peptide which contains more
than 20 amino acids. In some case, a polypeptide chain can be over a thousand amino acids long.
When amino acids join together in a peptide chain, they can now be known asamino acid residues.
Scientists can describe their specific location in the peptide by writing a number following the three- letter code of the amino acid. For example, ser-473 refers to the amino acidserinewhich is the 473rd amino acid in the amino acid sequence. The amino acid at the N-terminus is designated number 1. It is the genetic information contained in our genes which instruct our cells with the specific amino acid sequence for making new proteins.
Although there are only 20 amino acids, it is important to note that it is the combination of amino acids in the peptide sequence that gives each protein its distinct function. Indeed, this com- bination could exist as 20n alternatives, where n refers to the number of amino acids present in the polypeptide chain.
The sequence of amino acids which makes each specific protein can therefore be considered as sim- ilar to how letters of the alphabet can link together to form different words. There are only 26 letters in the standard alphabet, yet there are hundreds of thousands of words in the English language alone!
It is also important to consider that it only takes one amino acid to be out of its correct location for the protein to become potentially useless and dan- gerous. Indeed, the medical condition sickle cell
anaemia (an abnormal red blood cell shape which results in restricted blood flow to organs) results from the replacement ofglutamatewithvalineat the 6th position.
From an exercise science perspective, we are interested in knowing the specific locations of the amino acids serine, tyrosine and threonine, as these amino acids can be phosphorylated during exercise and this may therefore render the protein active or inactive. For example, the protein adenosine monophosphate kinase (AMPK) is phosphorylated at ser172 during exercise, and this protein is currently thought to be one of the regu- latory proteins involved in increasing muscle glu- cose uptake during exercise, as well as signalling training adaptation (Richter & Ruderman, 2009).
4.3.2 Secondary structure
The backbone of the polypeptide chain does not extend in a straight line for its entire length.
Instead, it repeatedly folds in a number of distinct forms, which ultimately gives rise to a three- dimensional structure. The secondary structure of a protein refers to the conformation of a short stretch of the polypeptide chain which can fold in two common forms known as thealpha helix or βpleated sheets (see Figure 4.5b).
In both forms of secondary structure, the protein is stabilized by hydrogen bonds which form at regular intervals along the polypeptide backbone between neighbouring elements such as oxygen.
The hydrogen bond is a form of non-covalent bond between a hydrogen atom with a partial positive charge and an oxygen or nitrogen atom with a partial negative charge. Although hydrogen bonds are considerably weaker than covalent bonds, the considerable number of bonds between hydrogen and oxygen atoms in peptide units allows suffi- cient force for the secondary structure of proteins to be stabilized.
4.3.3 Tertiary structure
The tertiary structure of a protein refers to the three- dimensional shape of the entire polypeptide chain
(see Figure 4.5c). It is only when the protein has folded to its tertiary structure that it is able to func- tion. Given the tertiary three-dimensional shape, it is possible for amino acids that are far apart in the primary structure to be now in close proximity.
Many types of chemical bonds are responsible for giving rise to the tertiary structure of proteins, the strongest of which is the covalent disulphide bond. Disulphide bonds are formed between the sul- phydryl groups of two monomers of the amino acid cysteine and are symbolized chemically as S-S.
Other more frequent but less strong bonds include hydrogen bonds, ionic bonds and hydrophobic interactions. The latter also help to shape the tertiary structure of proteins, given that some amino acids are attracted to water (i.e. hydrophilic), whereas others are repelled from water (i.e. hydrophobic). Given that most proteins exist in water environments inside our cells, those amino acids which are hydrophobic therefore reside deep in the central region of the protein, away from the protein’s surface, whereas the ‘water-loving’ hydrophilic amino acids reside nearer to the protein’s surface in contact with the cytoplasm.
Cellular stresses such as heat, free radical pro- duction and changes in pH can all disrupt the tertiary structures of proteins. In such instances, the protein is said to havedenaturedand has there- fore lost function. Fortunately, cells have a highly conserved family of proteins known asheat shock proteins (HSPs), which help to repair damaged and unfolded proteins in order to restore their function.
The stress of even moderate-intensity exercise can up-regulate muscle HSP content in the days fol- lowing the exercise protocol, and hence these pro- teins are thought to repair any damage to proteins induced by the exercise bout as well as protect the cell against future stresses (Mortonet al., 2006).
4.3.4 Quaternary structure
Some proteins are composed of more than one polypeptide chain and, in these instances, the protein is now considered to have a quater- nary structure (see Figure 4.5d), defined as the structural arrangement of each polypeptide chain
N
N
N
N
N N
H
H H
H H
H H
H
H
H
H
H
C C
C C
C C
C C C
C C C
C
C C
C C
C C
C C
C C
R
R
R
R
R R
R
R
R R R R
R
R
R
R
R
O O
O O
O
O O O
O O O
O
O
O
O
O
C C
C C
C N
N N
N
N
N N
N
N N
C
C C C
C C
N H
O
O O
O
O O
N
N
N N
N
H N H
H H H
H
H H
H H H
H H
H H
H
H H
H H H
H H
H
C
C C
C R
H C C
C R
HRC H
H
C C
R H H H
C R R
R
R C
C
H R O
N O C N
H
C H R C
C
C Amino
acids
Peptide bond
Hydrogen bond
Beta pleated sheet Alpha helix
(b) Secondary structure (twisting and folding of neighboring amino acids, stabilized by hydrogen bonds)
(c) Tertiary structure (three-dimensional shape of polypeptide chain) (a) Primary structure
(amino acid sequence) Polypeptide chain
(d) Quatemary structure (arrangement of two or more polypeptide chains)
O
Figure 4.5 Overview of protein structure. (a) Primary structure refers to the linear sequence of amino acids in the polypeptide chain. (b) Secondary structure of proteins: the repeated twisting and folding of neighbouring amino acids that are bonded by hydrogen bonds in common conformations known as the alpha helix and theβpleated sheets. (c) Tertiary structure refers to the 3-dimensional structure of the protein that has arisen during the protein folding process. (d) Quaternary structure exists for those proteins with two subunits or more and refers to the arrangement of each subunit relative to another. (adapted from Tortora and Derrickson,Principles of Anatomy and Physiology, Twelfth Edition, 2009, reproduced by permission of John Wiley & Sons Inc.)
(or subunit) relative to one another. The bonds that hold each subunit together are similar to those in the tertiary structure. One example of a protein with a quaternary structure is haemoglobin, the protein that is responsible for transporting oxygen in our blood to cells and tissues. Haemoglobin is
composed of four subunits, twoα-globin units and twoβ-globin units. Myosin, the protein involved in the contractile apparatus of muscle cells, is com- posed of six subunits, two of which are known as myosin heavy chainsand four of which are referred to asmyosin light chains.