Disulfide-dependent multimeric assembly of resistin family hormones.
Publication/Presentation Date
5-21-2004
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.
Volume
304
Issue
5674
First Page
1154
Last Page
1158
ISSN
1095-9203
Published In/Presented At
Patel, S. D., Rajala, M. W., Rossetti, L., Scherer, P. E., & Shapiro, L. (2004). Disulfide-dependent multimeric assembly of resistin family hormones. Science (New York, N.Y.), 304(5674), 1154–1158. https://doi.org/10.1126/science.1093466
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
15155948
Department(s)
Department of Pediatrics
Document Type
Article