Structural relationship of κ-type light chains with AL amyloidosis: multiple deletions found in a VκIV protein

Abstract

SUMMARY Two amyloidogenic Bence Jones proteins (Am37 VκIV and NIG1 VκI) and one non-amyloidogenic protein (NIG26 VκIII) were characterized. The protein Am37 had four deletions when compared with the translated germ-line gene sequence: two Ser residues following position 27 (27e, 27f) in CDR1 and two amino acids Pro-44, and Tyr-49 in FR2 were deleted. A strictly conserved salt-bridge-forming amino acid, Asp-82, was replaced by the hydrophobic residue Leu. In a comparative study of amyloidogenic and non-amyloidogenic proteins, five amino acids (Ser-10, Ala-13, Ser-65, Gln-90, and Ile-106) were found to be unique to NIG1 and several other amyloidogenic proteins. Additional substitutions also occur within these proteins. These substitutions might be significant in altering protein folding as well as in contributing to their aggregation as amyloid fibrils.