Structural characterization of κ II Inc, a new amyloid immunoglobulin

Light chain Inc, obtained from a patient with amyloid arthropathy, has an M_r of 23 550 and consists of 219 amino acid residues. The complete primary structure of its variable domain has been determined by sequence analysis of the corresponding tryptic peptides, aligned by fragments derived from cyanogen bromide digestion, and by partially sequencing the intact protein. Although closely related to protein of the V κ II subgroup, light chain Inc differs from its counterpart by the replacement of some invariant residues in its variable domain. By comparing its sequence with that of the nonamyloid κ II Nim, a different distribution of some polar and apolar amino acid residues through the molecule is evidenced. A computer graphic analysis shows that some of the replaced amino acid residues cannot be readily accomodated in the known three-dimensional structure of the immunoglobulin light chains.