The core cysteines, (C909) of islet antigen-2 and (C945) of islet antigen-2β, are crucial to autoantibody binding in type 1 diabetes.

ABSTRACT: Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA-2) autoantibodies (IA-2A), possibly through disulfide bond formation. We therefore investigated which cysteines are critical to IA-2A binding in patients with newly diagnosed type 1 diabetes. All 10 cysteines in the intracellular domain of IA-2 were modified to serine by site-directed mutagenesis, and the effects of these changes on autoantibody binding in comparison with wild-type control were investigated by radiobinding assay. Mutation of the protein tyrosine phosphatase (PTP) core cysteine (C909) in IA-2 caused large reductions in autoantibody binding. In contrast, little or no reduction in binding was seen following substitution of the other cysteines. Modification of the core cysteine (C945) in IA-2β als

SUBMITTER: Elvers KT 

PROVIDER: S-EPMC3526053 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature