| First Author | Zhang R | Year | 2018 |
| Journal | Chem Senses | Volume | 43 |
| Issue | 5 | Pages | 357-366 |
| PubMed ID | 29659735 | Mgi Jnum | J:262892 |
| Mgi Id | MGI:6187791 | Doi | 10.1093/chemse/bjy022 |
| Citation | Zhang R, et al. (2018) A Multispecific Investigation of the Metal Effect in Mammalian Odorant Receptors for Sulfur-Containing Compounds. Chem Senses 43(5):357-366 |
| abstractText | 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 odorant receptor (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 quantum mechanics/molecular mechanics (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 2 mouse MTMT receptors, and a third mouse MTMT receptor, Olfr15, that does not have a copper effect. We found that the function of all 3 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. |
