PRIMARY STRUCTURE OF PROTEIN & ITS SIGNIFICANCE

 Proteins are large molecules having a large 3 D structure, and their structure is organized at four different levels. They are:

 Primary Structure

Secondary Structure

Tertiary Structure

Quaternary Structure

Primary Structure

The primary structure denotes the linear sequential arrangement of amino acids.

Essential characteristics involved in the formation of the primary structure are:

1)   The sequence of amino acids:

• The genes decide the sequence of amino acids in a polypeptide chain
• Change in the sequence of the same amino acids changes the peptide bond's nature though it is made of the same amino acids
• e.g. – Gly-Val-Ala & Gly-Ala-Val.

2)   N and C terminal amino acids:

• The free amino group attached to the alpha carbon at one end of the polypeptide is called an amino-terminal end (-N terminal). The amino acid contributing to the amino group is called alpha-amino acid. It is numbered as the first amino acid.
• The amino group is written on the left-hand side of the polypeptide chain, and the protein synthesis starts from this point.
• The free carboxyl group attached to the alpha carbon at the other end of the polypeptide is called the carboxy-terminal end (-C terminal). It is numbered as the last amino acid.

3)Total number of amino acids

4)   4)Types and composition of amino acids

5)   5)Peptide bonds

• The bond formed between carboxy group of one amino acid & amino group of other amino acid is called as peptide bond
• The Peptide bond (C-N) is partial double bond in nature.
• The partial double bond character allows only partial folding of the protein
• The side chains attached on either side of the peptide bond cause restriction of the movement of the peptide bond.

    The spatial orientation of the protein structure is determined by the psi and phi angles.

• Psi angle(ϕ) is the angle between C_α - C, and 
• phi angle (ᵠ) is the angle between C_α -N 
• both these  angles of rotation are called as Ramachandran angles. 
• The rotation is possible only between these C-N bond and C-C bond and not around N-C due to steric hindrance.

6)   6)Disulfide bond :

• The bond formed between two sulfide groups of cysteine residues present at different regions of the polypeptide chain is disulfide bond.

       These disulfide bonds can be 

        -intra-chain ( bond within the same polypeptide chain ) & 

        -inter-chain (bond between different polypeptide chains)  

• Inter chain disulfide bridges produce branching points in the primary structure of protein.
• An example of such intra and inter-chain disulfide bond formation is the structure of insulin.

Significance of primary structure :

• The primary structure determines the higher organization of protein.
• The primary structure determines the biological activity, 

    -i.e., change in a single amino acid by a mutation in the linear sequence will lead to alteration in the function of the protein

    -e.g., Replacement of glutamic acid by valine at the 6^th position in hemoglobin changes from normal hemoglobin (HbA) to sickle cell hemoglobin (HbS)