Disulfide-dependent multimeric assembly of Resistin family hormones

Saurabh D. Patel, Michael W. Rajala, Luciano Rossetti, Philipp E. Scherer, Lawrence Shapiro

Research output: Contribution to journalArticlepeer-review

253 Scopus citations


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 RELMβ reveal an unusual multimeric structure. Each protomer comprises a carboxy-terminal disuiflde-rich β-sandwich "head" domain and an amino-terminal α-helical "tail" segment. The α-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.

Original languageEnglish (US)
Pages (from-to)1154-1158
Number of pages5
Issue number5674
StatePublished - May 21 2004

ASJC Scopus subject areas

  • General


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