Structural relationship of kappa-type light chains with AL amyloidosis: multiple deletions found in a V kappa IV protein

Two amyloidogenic Bence Jones proteins (Am37 V kappa IV and NIG1 V kappa I) and one non-amyloidogenic protein (NIG26 V kappa III) 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 CD R1 and two amino acids Pro-44, and Tyr-49 in FR2 were deleted. A strictly c onserved salt-bridge-forming amino acid, Asp-82, was replaced by the hydrop hobic residue Leu. In a comparative study of amyloidogenic and non-amyloido genic proteins, five amino acids (Ser-10, Ala-13, Ser-65, Gln-90, and Ile-1 06) were found to be unique to NIG1 and several other amyloidogenic protein s. Additional substitutions also occur within these proteins. These substit utions might be significant in altering protein folding as well as in contr ibuting to their aggregation as amyloid fibrils.