title: Conformational isomerism, rotational allomerism, and divergent evolution in immunoglobulin light chains.
abstract: Immunoglobulin light chains are examples of single polypeptide chains synthesized under the control of two genes. The three-dimensional structure of a human (Mcg) lambda-type chain (Bence-Jones) dimer supports the hypothesis of a common primordial gene for the amino ("variable" or V) and carboxyl ("constant" or C) halves of each monomer. However, sequence homologies have been obscurred by divergent evolution of the V and C regions ("domains"). The types of evolutionary changes that have occurred in the domain can be surmised by a comparison of the sequences, using the three-dimensional structures as a basis for alignment. Despite substantial differences in sequences, the hydrophobic character of key internal sites has been maintained in each domain. Regions present in only one domain are situated in position appropriate for their functions, but not deleterious to the general structural integrity of a common fold. The divergence of the V and C domains can be interpreted in terms of rotational allomerism. The cylinders of beta-pleated sheets have rotated in such a way that homologous regions in the two domains perform different functions in their interactions with a second molecule of light or heavy chain. These regions include complementarity-determining sites for antigen binding in the V domains and crossover sites stabilizing dimer formation in the C domains. Differences in surface properties between the V1-V2 and C1-C2 dimeric modules may partially explain why the V regions have been implicated in the formation of amyloid fibrils and in the characteristic thermal behavior of Bence-Jones proteins.
mesh_terms: D000595:Amino Acid Sequence; D005075:Biological Evolution; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D008961:Models, Structural; D009194:Myeloma Proteins; D011487:Protein Conformation
chemical_list: D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins