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 journalArticle

218 Citations (Scopus)

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 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
JournalScience
Volume304
Issue number5674
DOIs
StatePublished - May 21 2004

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Resistin
Disulfides
Hormones
Insulin
Liver
Protein Subunits
Adipocytes
Insulin Resistance
Obesity
Head
Serum

ASJC Scopus subject areas

  • General

Cite this

Patel, S. D., Rajala, M. W., Rossetti, L., Scherer, P. E., & Shapiro, L. (2004). Disulfide-dependent multimeric assembly of Resistin family hormones. Science, 304(5674), 1154-1158. https://doi.org/10.1126/science.1093466

Disulfide-dependent multimeric assembly of Resistin family hormones. / Patel, Saurabh D.; Rajala, Michael W.; Rossetti, Luciano; Scherer, Philipp E.; Shapiro, Lawrence.

In: Science, Vol. 304, No. 5674, 21.05.2004, p. 1154-1158.

Research output: Contribution to journalArticle

Patel, SD, Rajala, MW, Rossetti, L, Scherer, PE & Shapiro, L 2004, 'Disulfide-dependent multimeric assembly of Resistin family hormones', Science, vol. 304, no. 5674, pp. 1154-1158. https://doi.org/10.1126/science.1093466
Patel, Saurabh D. ; Rajala, Michael W. ; Rossetti, Luciano ; Scherer, Philipp E. ; Shapiro, Lawrence. / Disulfide-dependent multimeric assembly of Resistin family hormones. In: Science. 2004 ; Vol. 304, No. 5674. pp. 1154-1158.
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