Primary Structure of the Variable Part of an Amyloidogenic Bence-Jones Protein (Mev.). An Unusual Insertion in the Third Hypervariable Region of a Human κ-Immunoglobulin Light Chain

Abstract

The complete amino acid sequence of the variable region of Bence-Jones protein Mev. from a patient suffering from multiple myeloma and generalized amyloidosis is presented. The amino acid sequence of the Bence-Jones protein Mev. is related to other human .kappa.-Ig L chains of subgroup I. With Val established in position 191 of the constant region, it is of the Inv (3) allotype. Two types of the Bence-Jones protein Mev. were found, one beginning with the typical N-terminal Asp and another lacking the N-terminal tripeptide and commencing with Met in position 4. A unique insertion of Glu after position 95 was found in the Bence-Jones protein. This is the position where the V- and J-gene segments join. The J-region of Bence-Jones protein Mev. exhibits some marked differences to the 5 J-regions recently established by nucleic acid sequencing. Apparently, there is considerable polymorphism in human .kappa.-J-genes. The amyloid fibril protein from the same patient (A Mev.) was also sequenced up to position 27. It was identical to the sequence of Bence-Jones protein Mev. commencing with Asp. The molecular mass of the amyloid fibril protein was between 11,000 and 12,000 Da [dalton] as estimated by gel filtration and dodecyl sulfate-polyacrylamide electrophoresis.