Four structural risk factors identify most fibril-forming kappa light chains.

Journal Article · Fri Sep 01 04:00:00 EDT 2000 · Amyloid : Int. J. Exp. Clin. Invest.

DOI:https://doi.org/10.3109/13506120009146835· OSTI ID:942802

Stevens, F J

Antibody light chains (LCs) comprise the most structurally diverse family of proteins involved in amyloidosis. Many antibody LCs incorporate structural features that impair their stability and solubility, leading to their assembly into fibrils and to their subsequent pathological deposition when produced in excess during multiple myeloma and primary amyloidosis. The particular amino acid variations in antibody LCs that account for fibril formation and amyloidogenesis have not been identified. This study focuses on amyloidogenesis within the Kl family of human LCs. Reanalysis of the current database of primary structures of proteins from more than 100 patients who produced Kl LCS, 37 of which were amyloidogenic, reveals apparent structural features that may contribute to amyloidosis. These features include loss of conserved residues or the gain of particular residues through mutation at sites involving a repertoire of approximately 20% of the amino acid positions in the light chain variable domain (V{sub L}). Moreover, 80% of all K1 amyloidogenic V{sub L}s are identifiable by the presence of at least one of three single-site substitutions or the acquisition of an N-linked glycosylation site through mutations. These findings suggest that it is feasible to predict fibril propensity by analysis of primary structure.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: SC
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 942802
• Report Number(s): ANL/BIO/JA-34752
• Journal Information: Amyloid : Int. J. Exp. Clin. Invest., Journal Name: Amyloid : Int. J. Exp. Clin. Invest. Journal Issue: 3 ; Sep. 2000 Vol. 7; ISSN 1744-2818
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
AMINO ACIDS
ANTIBODIES
CHAINS
IMMUNE SYSTEM DISEASES
MUTATIONS
PATIENTS
PROTEINS
RESIDUES
SOLUBILITY
STABILITY
VARIATIONS