| First Author | Patel SD | Year | 2004 |
| Journal | Science | Volume | 304 |
| Issue | 5674 | Pages | 1154-8 |
| PubMed ID | 15155948 | Mgi Jnum | J:90632 |
| Mgi Id | MGI:3044316 | Doi | 10.1126/science.1093466 |
| Citation | Patel SD, et al. (2004) Disulfide-dependent multimeric assembly of resistin family hormones. Science 304(5674):1154-8 |
| abstractText | 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. |
