Immunoglobulin Structure and Function in a nutshell

The two principal structures of immunoglobulins are now available in the Gallery. The trans form is the stable form in the absence of antigen, while the cis form is stable in the presence of antigen and complement. The two forms are quaternary isomers, differing almost only in the arrangement of subunits. It is now possible to give names to the various domains that suggest their shapes and functions. The word "elbow" is already used to describe the short flexible linking sequences between domains and the word "bridge" is already used to describe the longer flexible sequence in the middle of the heavy chain. These names can be retained. The light chain has two domains separated by an elbow of residues 104-109. Residues 1-103, previously named N_L, can now be named "antigen jaw_L", while residues 110-214, previously named C_L can be named "left-hand_L". The heavy chain domains can be similarly renamed (old names in parentheses): 1-111 "antigen jaw_H" (N_H); 114-230 "left-hand_H" (C_H1); 232-243 "bridge" or now possibly "latch"; 244-357 "right-hand" (C_H2); and 365-478 "complement jaw" (C_H3). Elbows are 112-113 and 358-364. The orientational relationship between a jaw and a left-hand is similar to that seen in the L chain of IgG2 (1YEF.pdb). Left hands clasp each other to form the antigen-binding complex, with the Complementarity Determining Regions on the inner surfaces of the jaws. Right-hands clasp right-hands to form the complement-binding complex. The switch between isomers involves four disulfide bridges exchanging partners, first the disulfides linking “left-hands” and then the disulfides in the “bridge”. This last exchange of disulfide partners may serve to lock the complement-binding domains into their binding conformation – hence the “bridge” may be better described as a “latch”. More work required!