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A Multispecific Investigation of the Metal Effect in Mammalian Odorant Receptors for Sulfur-containing Compounds.
Chem Senses. 2018 Apr 06;:
Authors: Zhang R, Pan Y, Ahmed L, Block E, Zhang Y, Batista VS, Zhuang H
Abstract
Metal-coordinating compounds are generally known to have strong smells, a phenomenon that can be attributed to the fact that odorant receptors for intense-smelling compounds, such as those containing sulfur, may be metalloproteins. We previously identified a mouse OR, Olfr1509, that requires copper ions for sensitive detection of a series of metal-coordinating odorants, including (methylthio)methanethiol (MTMT), a strong-smelling component of male mouse urine that attracts female mice. By combining mutagenesis and QM/MM modeling, we identified candidate binding sites in Olfr1509 that may bind to the copper-MTMT complex. However, whether there are other receptors utilizing metal ions for ligand-binding and other sites important for receptor activation is still unknown. In this study, we describe a second mouse OR for MTMT with a copper effect, namely Olfr1019. In an attempt to investigate the functional changes of metal-coordinating ORs in multiple species and to decipher additional sites involved in the metal effect, we cloned various mammalian orthologs of the two mouse MTMT receptors, and a third mouse MTMT receptor, Olfr15, that does not have a copper effect. We found that the function of all three MTMT receptors varies greatly among species and that the response to MTMT always co-occurred with the copper effect. Furthermore, using ancestral reconstruction and QM/MM modeling combined with receptor functional assay, we found that the amino acid residue R260 in Olfr1509 and the respective R261 site in Olfr1019 may be important for receptor activation.
PMID: 29659735 [PubMed - as supplied by publisher]
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