|Entry||Database: EMDB / ID: 7121|
|Title||Cryo-EM structure of human TRPV6 in amphipols|
|Map data||primary map|
|Sample||TRPV6 ion channel in open states|
|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 / response to calcium ion / Ankyrin repeats (3 copies) / 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
|Source||Homo sapiens / / human|
|Method||Cryo EM / single particle reconstruction / 4 Å resolution|
|Authors||McGoldrick LL / Singh AK|
|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.
|Validation Report||PDB-ID: 6bo9|
SummaryFull reportAbout validation report
|Date||Deposition: Nov 18, 2017 / Header (metadata) release: Dec 6, 2017 / Map release: Dec 20, 2017 / Last update: Jan 24, 2018|
Downloads & links
|File||emd_7121.map.gz (map file in CCP4 format, 33959 KB)|
|Projections & slices|
Images are generated by Spider package.
|Voxel size||X=Y=Z: 0.98 Å|
CCP4 map header:
-Entire TRPV6 ion channel in open states
|Entire||Name: TRPV6 ion channel in open states / Number of components: 2|
-Component #1: protein, TRPV6 ion channel in open states
|Protein||Name: TRPV6 ion channel in open states / Recombinant expression: No|
|Source||Species: Homo sapiens / / human|
|Source (engineered)||Expression System: Hek-293 cells|
-Component #2: protein, Transient receptor potential cation channel subfamily V ...
|Protein||Name: Transient receptor potential cation channel subfamily V member 6|
Recombinant expression: No
|Mass||Theoretical: 85.168953 kDa|
|Source (engineered)||Expression System: Homo sapiens / / human|
|Specimen||Specimen state: particle / Method: Cryo EM|
|Sample solution||Specimen conc.: 0.3 mg/ml / Buffer solution: TRIS, NaCl, / pH: 8|
|Vitrification||Cryogen name: ETHANE / Temperature: 277 K / Humidity: 100 %|
-Electron microscopy imaging
Model: Tecnai F30 / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI F30|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 67 e/Å2 / Illumination mode: SPOT SCAN|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 65259|
|3D reconstruction||Software: RELION / Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF|
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