title: Effect of methionine oxidation on the structural properties, conformational stability, and aggregation of immunoglobulin light chain LEN.
abstract: Light chain amyloidoses arise from the overproduction and abnormal deposition of the immunoglobulin light chain in various organs. LEN is the variable domain of an immunoglobulin light chain originally isolated from the urine of a patient suffering from multiple myeloma, with no sign of renal dysfunction or amyloidosis. LEN was shown to form fibrils in vitro under mildly destabilizing conditions. In this work, we investigated the changes induced by methionine oxidation in the structural properties, conformational stability, and aggregation behavior of immunoglobulin light chain domain LEN. We established that LEN was well-protected from oxidation in its native state, but successful oxidation was achieved in the presence of 4 M GuHCl. Oxidation induced noticeable structural changes in LEN and destabilized this protein. The methionine-oxidized LEN preferred to form amorphous aggregates instead of fibrils. The results indicated that the LEN oxidation may play an important role in amorphous deposition of the protein, but not in its fibrillation.
authors.affiliation: Department of Chemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Hu
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Qin
authors.forename: Bin
authors.initials: B
authors.lastname: Xue
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Fink
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008715:Methionine / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013997:Time Factors
chemical_list: D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D008715:Methionine