|Entry||Database: PDB / ID: 6bo8|
|Title||Cryo-EM structure of human TRPV6 in nanodiscs|
|Components||Transient receptor potential cation channel subfamily V member 6|
|Keywords||TRANSPORT PROTEIN / Ion channel / Membrane protein|
|Function/homology||Transient receptor potential channel, vanilloid 6 / Transient receptor potential cation channel subfamily V member 5/6 / calcium ion import across plasma membrane / TRP channels / Transient receptor potential cation channel subfamily V / Transient receptor potential channel / regulation of calcium ion-dependent exocytosis / calcium ion homeostasis / Ankyrin repeat / calcium channel activity ...Transient receptor potential channel, vanilloid 6 / Transient receptor potential cation channel subfamily V member 5/6 / calcium ion import across plasma membrane / TRP channels / Transient receptor potential cation channel subfamily V / Transient receptor potential channel / regulation of calcium ion-dependent exocytosis / calcium ion homeostasis / Ankyrin repeat / calcium channel activity / calcium ion transmembrane transport / Ion transport domain / calcium ion transport / Ion transport protein / Ankyrin repeat profile. / Ankyrin repeat / Ankyrin repeat region circular profile. / Ankyrin repeat-containing domain / Ankyrin repeat-containing domain superfamily / Ankyrin repeats (3 copies) / response to calcium ion / calmodulin binding / integral component of plasma membrane / extracellular exosome / plasma membrane / metal ion binding / Transient receptor potential cation channel subfamily V member 6|
Function and homology information
|Specimen source||Homo sapiens / human /|
|Method||Electron microscopy (3.6 Å resolution / Particle / Single particle) / Transmission electron microscopy|
|Authors||McGoldrick, L.L. / Singh, A.K. / Saotome, K. / Yelshanskaya, M.V. / Twomey, E.C. / Grassucci, R.A. / Sobolevsky, A.I.|
|Citation||Journal: Nature / Year: 2018|
Title: Opening of the human epithelial calcium channel TRPV6.
Authors: Luke L McGoldrick / Appu K Singh / Kei Saotome / Maria V Yelshanskaya / Edward C Twomey / Robert A Grassucci / Alexander I Sobolevsky
Abstract: Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with ...Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with a variety of human diseases, including cancers. TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside; it increases substantially in the presence of phosphatidylinositol 4,5-bisphosphate. Crystal structures of detergent-solubilized rat TRPV6 in the closed state have previously been solved. Corroborating electrophysiological results, these structures demonstrated that the Ca selectivity of TRPV6 arises from a ring of aspartate side chains in the selectivity filter that binds Ca tightly. However, how TRPV6 channels open and close their pores for ion permeation has remained unclear. Here we present cryo-electron microscopy structures of human TRPV6 in the open and closed states. The channel selectivity filter adopts similar conformations in both states, consistent with its explicit role in ion permeation. The iris-like channel opening is accompanied by an α-to-π-helical transition in the pore-lining transmembrane helix S6 at an alanine hinge just below the selectivity filter. As a result of this transition, the S6 helices bend and rotate, exposing different residues to the ion channel pore in the open and closed states. This gating mechanism, which defines the constitutive activity of TRPV6, is, to our knowledge, unique among tetrameric ion channels and provides structural insights for understanding their diverse roles in physiology and disease.
SummaryFull reportAbout validation report
|Date||Deposition: Nov 18, 2017 / Release: Dec 20, 2017|
Downloads & links
A: Transient receptor potential cation channel subfamily V member 6
B: Transient receptor potential cation channel subfamily V member 6
C: Transient receptor potential cation channel subfamily V member 6
D: Transient receptor potential cation channel subfamily V member 6
Mass: 85168.953 Da / Num. of mol.: 4 / Source: (gene. exp.) Homo sapiens / human / / Gene: TRPV6, ECAC2 / Production host: Homo sapiens / References: UniProt:Q9H1D0
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: SINGLE PARTICLE|
|Component||Name: TRPV6 ion channel in open states / Type: COMPLEX / Entity ID: 1 / Source: RECOMBINANT|
|Molecular weight||Experimental value: NO|
|Source (natural)||Organism: Homo sapiens|
|Source (recombinant)||Organism: HEK-293 cells|
|Buffer solution||Details: TRIS, NaCl, / pH: 8|
|Specimen||Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Grid material: GOLD / Grid type: C-flat-1.2/1.3|
|Vitrification||Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 kelvins|
-Electron microscopy imaging
Model: Tecnai F30 / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TECNAI F30|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN|
|Electron lens||Mode: BRIGHT FIELD|
|Image recording||Electron dose: 67 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Image scans||Movie frames/image: 40|
|Software||Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement|
|EM software||Name: RELION / Category: RECONSTRUCTION|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Particle selection||Number of particles selected: 509569|
|3D reconstruction||Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 46124 / Symmetry type: POINT|
|Refine LS restraints|
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