title: Structure of the full-length TRPV2 channel by cryo-EM.
abstract: Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Wood Building, W151D, Cleveland, Ohio 44106, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Huynh
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Wood Building, W151D, Cleveland, Ohio 44106, USA.|Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cohen
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.|California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: Jiansen
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Wood Building, W151D, Cleveland, Ohio 44106, USA.|Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Samanta
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Wood Building, W151D, Cleveland, Ohio 44106, USA.|Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Lodowski
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.|California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Wood Building, W151D, Cleveland, Ohio 44106, USA.|Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Vera Y
authors.initials: VY
authors.lastname: Moiseenkova-Bell
mesh_terms: D000818:Animals; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D007477:Ions; D008055:Lipids / Q000737:chemistry; D010539:Permeability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D007477:Ions; D008055:Lipids; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C476722:Trpv2 protein, rat