title: Structure of the TRPV1 ion channel determined by electron cryo-microscopy.
abstract: Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.
authors.affiliation: 1] Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517, USA [2].
authors.forename: Maofu
authors.initials: M
authors.lastname: Liao
authors.forename: Erhu
authors.initials: E
authors.lastname: Cao
authors.forename: David
authors.initials: D
authors.lastname: Julius
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat; D020285:Cryoelectron Microscopy; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D051381:Rats; D050916:TRPV Cation Channels / Q000737:chemistry*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat