Antonín Vítek

Analysis of interspecies variability of immunoglobulin lambda chains reveals differences in domain tertiary structures

Abstract X-ray crystallography showed the NH 2 -proximal (variable, V) and COOH-proximal (constant, C) halves of the λ chain to fold independently into autonomous three-dimensional domains, homologous domains from different chains interacting strongly by non-covalent forces to form domain dimers. In this letter, interspecies homology of five immunoglobulin λ chain primary structures from man, mouse and pig has been evaluated separately for those segments of polypeptide chains that correspond to basic structural elements of a domain fold. The highest degree of phylogenetic conservation has always been found with segments forming the innermost part of domain dimers, though the V-V dimer is known to be packed inside out with respect to the C-C dimer, its inner segments being different from those of the C-C dimer. Differences of interspecies homology between analogous segments from the variable and the constant domain have been revealed which correlate with differences in domain architectures. Two different measures of interspecies homology have been defined (% positions with identical residues; % positions displaying 80% homology) the ratio of which is indicative of packing density and of folding constraints imposed on a particular segment.