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We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels. The third transmembrane helix S3 is remarkably long, shaping a unique transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli. We identified two lipid-binding sites, one being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to the ion-conducting pore, where the conserved LWF motif of the TRPC family is located.<\/jats:p>","DOI":"10.7554\/elife.36852","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T08:00:11Z","timestamp":1525420811000},"source":"Crossref","is-referenced-by-count":139,"title":["Structure of the human lipid-gated cation channel TRPC3"],"prefix":"10.7554","volume":"7","author":[{"given":"Chen","family":"Fan","sequence":"first","affiliation":[{"name":"Van Andel Institute, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wooyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Van Andel Institute, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinan","family":"Sun","sequence":"additional","affiliation":[{"name":"Vollum 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