Antibody

From DrugPedia: A Wikipedia for Drug discovery

Antibody are immune system-related proteins called immunoglobulins. Soluble, or secreted, antibody is structurally slightly different than the antibody on the surface of B cells but the antigen recognition sites are similar. The ability of antibodies to recognize specific antigen is an important characteristic .

Antigen recognition and binding allows antibodies to perform three important functions.

• opsonization
• activating complement
• neutralizing toxins and toxic organisms

Antibody Structure

Each antibody consists of four polypeptides– two heavy chains and two light chains linked by disulphide bonds to form a "Y" shaped molecule.

The amino acid sequence in the tips of the "Y" varies greatly among different antibodies. This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen. The variable region includes the ends of the light and heavy chains. Treating the antibody with a protease can cleave this region, producing Fab or fragment antigen binding that include the variable ends of an antibody. Material used for the studies shown below originated from Fab.

The constant region determines the mechanism used to destroy antigen.

The light chain has two domains and the heavy has four. The N-terminal domain at the tip of the arms of the "Y" on both the heavy and light chain are known to be variable in amino acid sequence composition and are thus called variable domains (VL and VH). The other domains are called constant for a similar reason (CL, CH1, CH2, CH3).

The variable domains show three regions of hypervariability in sequence called the complementarity determining regions (CDRs). They differ in length and sequence between different antibodies and are mainly responsible for the specificity (recognition) and affinity (binding) of the antibodies to their target markers. Proteolytic digestion of antibodies releases different fragments termed Fv (Fragment variable), Fab (Fragment antigen binding) and Fc (Fragment crystallisation).

The linear protein chain in each of the domains folds into a characteristic 3D structure called the immunoglobulin fold. It consists of two sheets, formed by the protein chain, packed against each other. In the constant domains, each sheet consists of three and four strands respectively. The constant domains of the Fc fragment are responsible for mediating the effector functions of the antibody. The variable domain has a similar structure, except that there are nine strands; four and five in each sheet respectively.