Question

answer 2a and 2 b

2. A) What are the variable domains on antibodies and what do they do? Explain why and how the variation in Vi and VH domains of immunoglobulins is largely confined to the hypervariable loops.

Answer 1

(a) Antibodies are the molecules that binds to the antigen entering into the body thus triggering an immune response. These immune response triggering molecules are also known as immunoglobulins. Each of the antibody consists of many four polypeptides: two light chains and two heavy chains which are joined together. There are mainly two major domains for the immunoglobulins: Variable domains and Constant domain.

The variable domain or region is further classified into two: (1) hypervariable region and (2) framework region.

Hypervariable regions: These regions at a given position have a higher ratio of different amino acids, relative to the most common amino acid at that given region. There are mainly three hypervariable regions for both the heavy and light chains, i.e, HV1, HV2 and HV3. These Hypervariable regions are also known as the complementarity determining regions(CDRs) since these regions directly contact to a portion of the antigen's surface.

Framework regions: The light as well as the heavy chains have four framework regions which consists of more stable amino acid sequences which separates the HV regions. These regions mainly form a beta sheet structures that acts as a scaffold to hold the HV regions.

(b) The V_L and V_H domains of the immunoglobulins have similar homologous structures each of which consist of the beta-pleated sheets which are packed face to face order with the main chains of each of the domains about 10A^o apart and are inclined to an angle of -30⁰. These beta pleated sheets of each of the domains are mainly linked to each other by a conserved disulfide bridge.

The hypervariable loops are mainly located on the surface of these domains, this helps the loops to tolerate more of the amino acid substitutions. The V_L and V_H domains which are highly confined to the hypervariable loops thus is arranged so to tolerate more amino acid substitutions and the changes in the amino acids on beta pleated sheets could result in the destabilization of these domains.