{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:41:13Z","timestamp":1792712473629,"version":"4.5.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,2,28]]},"abstract":"<jats:p>\n                    Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methylthio)methanethiol (MeSCH\n                    <jats:sub>2<\/jats:sub>\n                    SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol\u2013OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling\n                    <jats:italic>trans<\/jats:italic>\n                    -cyclooctene) among &gt;125 compounds tested. Copper chelator (tetraethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmembrane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT\u2013copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1111297109","type":"journal-article","created":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T20:49:22Z","timestamp":1328906962000},"page":"3492-3497","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":111,"title":["Crucial role of copper in detection of metal-coordinating odorants"],"prefix":"10.1073","volume":"109","author":[{"given":"Xufang","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;"},{"name":"Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine\/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Block","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Connelly","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubo","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of 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China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siji","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; 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