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- Title
Disulfide-dependent multimeric assembly of resistin family hormones.
- Authors
Patel, Saurabh D; Rajala, Michael W; Rossetti, Luciano; Scherer, Philipp E; Shapiro, Lawrence
- Abstract
Resistin, founding member of the resistin-like molecule (RELM) hormone family, is secreted selectively from adipocytes and induces liver-specific antagonism of insulin action, thus providing a potential molecular link between obesity and diabetes. Crystal structures of resistin and RELMbeta reveal an unusual multimeric structure. Each protomer comprises a carboxy-terminal disulfide-rich beta-sandwich "head" domain and an amino-terminal alpha-helical "tail" segment. The alpha-helical segments associate to form three-stranded coiled coils, and surface-exposed interchain disulfide linkages mediate the formation of tail-to-tail hexamers. Analysis of serum samples shows that resistin circulates in two distinct assembly states, likely corresponding to hexamers and trimers. Infusion of a resistin mutant, lacking the intertrimer disulfide bonds, in pancreatic-insulin clamp studies reveals substantially more potent effects on hepatic insulin sensitivity than those observed with wild-type resistin. This result suggests that processing of the intertrimer disulfide bonds may reflect an obligatory step toward activation.
- Publication
Science (New York, N.Y.), 2004, Vol 304, Issue 5674, p1154
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1093466