Proteins and their structure

Proteins and their structure

Proteins are made up of the 20 different amino acids. These amino acids are joined together by a covalent linkage commonly known as a peptide bond. The linear sequence of these linked amino acids is specific for a protein. The amino acid sequence contains necessary information for that protein to fold into a unique three dimensional structure and correspondingly a unique function. The structure of proteins can be best understood by considering them in four hierarchical levels as described in figure 3.7

1. The primary structure of proteins

The amino acid sequence of a protein is known as its primary structure. Knowing the primary structure for a protein is important because even small changes (due to mutations) in the primary structure can lead to improper folding and hence impairment or complete loss of function.

Peptide bonds

The amino acids in protein are covalently linked together to form peptide bonds. Peptide bonds are amide linkages between the α carboxyl group of one amino acid and the amino group of another amino acid. For example, serine and alanine can form a peptide called serylalanine as described in figure 3.8. Since two amino acids are joined together, this molecule is known as a dipeptide. If many amino acids are joined together in the same way to form a single chain, such a chain is known as a polypeptide. The atoms excluding the side chains of amino acids in a polypeptide are known together as the back bone or main chain of the polypeptide.

Peptide bonds have some important properties, which are

a.  Peptide bonds are generally in trans conformation. However in rare conditions peptide bonds formed by proline can adopt a cis conformation.

b.  Peptide bonds have a partial double bond character, which gives them a planar nature and hence cannot be rotated.

c.   Since peptide bonds are amide linkages the –C=O and –NH groups cannot donate or accept protons and are uncharged. The net charge of a polypeptide can come only from the N terminus amino group, C terminus carboxyl group and the side chains of the amino acids.

d.  Despite not being ionisable, the –C=O and –NH groups of peptide bonds are polar and can involve in the formation of hydrogen bonds. This property is important for the formation of secondary structures of proteins.

2. Secondary structure of proteins

The back bone of a polypeptide forms regular structural arrangements by making hydrogen bonds with its neighbouring amino acids. As a rule, these hydrogen bonds are always between the main chain –NH group and –C=O group. There are three main types of secondary structures present in proteins namely α Helix, β sheet and β turn.

Hydrogen Bonds

Hydrogen bonds are weak electrostatic interactions between an electro negative atom and a hydrogen which is covalently linked to another electro negative atom.

α Helix

It is a spiral (helical) structure of a tightly packed and coiled main chain of a polypeptide with the side chain groups of amino acids protruding outside. The helical structure is achieved by the formation of hydrogen bonds between the –C=O of an n^th amino acid with the –NH group of n+4^th amino acid. Each turn of an α helix contains 3.6 amino acids.The α helices are mostly right handed but there are rare instances where left handed α helices are also present in proteins. The amino acid Proline can produce a kink in an α helix as its secondary amino group is not geometrically compatible inside an α helix.

β pleated sheets

In a β pleated sheet, two or more segments of a polypeptide chain line up next to each other forming a sheet like structure held together by hydrogen bonds. The strands of a β pleated sheet may be parallel where the N- and C- termini of the strands match up or antiparallel where the N-terminus of one strand is positioned next to the C-terminus of the other.

β turns

These are secondary structural elements with four amino acids that can reverse (turn) the direction of a polypeptide and thus help the polypeptide to form a globular shape. They are mostly found on the surface of proteins. The amino acids proline and glycine are more frequently found in β turns. They are also mostly found to connect two different α helices or β strands to form super secondary structure motifs such as helix-turn helix, beta meander, beta barrel etc.

3. Tertiary structure

The polypeptide folds in such a way that the secondary structure elements are packed compactly to form an overall three-dimensional structure called its tertiary structure. The tertiary structure is stabilized mainly by the interactions between the R groups (side chains) of the amino acids.

The interactions that contribute to tertiary structure are hydrogen bonds, ionic interactions, dipole-dipole interactions and Vander Waals Forces. The above mentioned interactions are also known as non bonded interactions.

The side chains with like charges such as Lys and Arg repel one another, while those with opposite charges such as Lys and Asp can form an ionic interaction. Similarly, polar R groups can form hydrogen bonds and other dipole-dipole interactions.

The amino acids with non polar, hydrophobic R groups cluster together on the inside of the protein through hydrophobic interactions. This cluster is also known as the hydrophobic core and it is an important feature of globular proteins. Similarly, the hydrophilic amino acids, (i.e.) the amino acids with side chains containing charged groups are present on the surface of globular proteins to interact with surrounding water molecules.

The sulphur containing side chains of two cysteine residues can form a covalent bond known as a disulfide bond. The disulfide bonds help to bring together two different parts of the same polypeptide or two different polypeptides together and are the only covalent interactions involved in the formation of tertiary structure.

4. Quaternary structure of proteins

Proteins that are made up of a single polypeptide chain have only three levels of structure. Some proteins are made up of more than one polypeptide chain. In such cases the tertiary structures formed by each of those polypeptide chains come together to form a quaternary structure. These individual polypeptide chains are also known as subunits. Hemoglobin, a protein which carries oxygen in blood is made up of four subunits. Similarly, DNA polymerase, an enzyme which synthesizes new strands of DNA is composed of ten subunits. The same types of interactions that contribute to tertiary structure are also involved in stabilization of the quaternary structure.