Chemical structure of light chains: amino acid sequence of type K Bence-Jones proteins

Abstract

Bence-Jones proteins are the light chains of the autologous myeloma globulin and are analogous to the light chains of normal human immunoglobulins. Peptide mapping has demonstrated that Bence-Jones proteins share a fixed portion of their sequence (the ‘constant’ portion) and also have a mutable part (the ‘variable’ portion). Sequence analysis and ordering of the tryptic and chymotryptic peptides has provided the tentative complete amino acid sequence of one Bence-Jones protein of antigenic type K. Comparison with partial sequence data for other type K Bence-Jones proteins has revealed many structural differences in the amino terminal half of the molecules, but only one structural difference in the carboxyl terminal half. The latter is strongly correlated with the Inv genetic factor. The points of interchange in the amino terminal half occur in clusters close to the half cystine residues and the ‘switch peptide’ (positions 102 through 105), after which the sequence becomes essentially invariant. This suggests that the major areas subject to sequence variation are part of a single topographical region which may define a portion of the antigen combining site in the light chains of antibodies. Many, but not all, the amino acid interchanges are compatible with a single point mutation. As yet, no single mutational theory suffices to explain the manifold differences in structure of the light chains. Such structural variation, however, could result from the presence of many related genes.