Dimerization of resistin and resistin-like molecules is determined by a single cysteine

Resistin is a peptide hormone secreted by adipocytes, Cysteine residues com prise 11 of 94 (12%) amino acids in resistin, The arrangement of these cyst eines is unique to resistin and its recently discovered family of tissue-sp ecific secreted proteins, which have been independently termed resistin-lik e molecules (RELMs) and the FIZZ (found in inflammatory zone) family. Here we show that resistin is a disulfide-linked homodimer that can be converted to a monomer by reducing conditions. The intestine-specific RELM beta has similar characteristics. Remarkably, however, the adipose-enriched RELM alp ha is a monomer under non-reducing conditions. We note that RELM alpha lack s a cysteine residue, closest to the cleaved N terminus, that is present in resistin and RELM beta in multiple species. Conversion of this cysteine to alanine abolishes dimerization of resistin, Thus, a single disulfide bond is necessary to connect two resistin subunits in a homodimer. The additiona l 10 cysteines most likely participate in intramolecular disulfide bonds th at define the conserved structure of the family members. The monomeric natu re of RELM alpha suggests structural and potentially functional divergence between resistin and this close family member.