Dimerization of resistin and resistin-like molecules is determined by a single cysteine.
Resistin is a peptide hormone secreted by adipocytes. Cysteine residues comprise 11 of 94 (12%) amino acids in resistin. The arrangement of these cysteines is unique to resistin and its recently discovered family of tissue-specific secreted proteins, which have been independently termed resistin-like 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 alpha is a monomer under non-reducing conditions. We note that RELM alpha lacks 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 additional 10 cysteines most likely participate in intramolecular disulfide bonds that define the conserved structure of the family members. The monomeric nature of RELM alpha suggests structural and potentially functional divergence between resistin and this close family member.
Banerjee
R R
RR
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Lazar
M A
MA
D017667:Adipocytes / Q000378:metabolism; D000595:Amino Acid Sequence; D003545:Cysteine; D019281:Dimerization; D006729:Hormones, Ectopic / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor; D011487:Protein Conformation; D011506:Proteins; D052243:Resistin
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D052243:Resistin; C413576:Retnla protein, mouse; D020932:Nerve Growth Factor; D003545:Cysteine