title: Structural insight into the assembly of TRPV channels.
abstract: Transient receptor potential (TRP) proteins are a large family of polymodal nonselective cation channels. The TRP vanilloid (TRPV) subfamily consists of six homologous members with diverse functions. TRPV1-TRPV4 are nonselective cation channels proposed to play a role in nociception, while TRPV5 and TRPV6 are involved in epithelial Ca²⁺ homeostasis. Here we present the cryo-electron microscopy (cryo-EM) structure of functional, full-length TRPV2 at 13.6 Å resolution. The map reveals that the TRPV2 cytoplasmic domain displays a 4-fold petal-like shape in which high-resolution N-terminal ankyrin repeat domain (ARD) structures can be unambiguously fitted. Fitting of the available ARD structures for other TRPV subfamily members into the TRPV2 EM map suggests that TRPV subfamily members have highly homologous structural topologies. These results allowed us to postulate a structural explanation for the functional diversity among TRPV channels and their differential regulation by proteins and ligands.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Huynh
authors.affiliation: Deparment of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cohen
authors.affiliation: Deparment of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Chakrapani
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Holdaway
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Deparment of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: vxm102@case.edu.
authors.forename: Vera Y
authors.initials: VY
authors.lastname: Moiseenkova-Bell
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D020285:Cryoelectron Microscopy; D007477:Ions; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D051381:Rats; D012441:Saccharomyces cerevisiae; D050916:TRPV Cation Channels / Q000737:chemistry*
chemical_list: D017487:Ankyrins; D007477:Ions; D008024:Ligands; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat; D002118:Calcium