|Entry||Database: EMDB / ID: 7009|
|Title||Structure of an acid sensing ion channel in a resting state at high pH|
|Sample||Acid Sensing Ion Channel 1a|
|Function/homology||acid-sensing ion channel activity / Epithelial sodium channel, chordates / sensory perception of sour taste / Epithelial sodium channel, conserved site / Epithelial sodium channel / Amiloride-sensitive sodium channels signature. / Amiloride-sensitive sodium channel / Stimuli-sensing channels / negative regulation of neurotransmitter secretion / cellular response to pH ...acid-sensing ion channel activity / Epithelial sodium channel, chordates / sensory perception of sour taste / Epithelial sodium channel, conserved site / Epithelial sodium channel / Amiloride-sensitive sodium channels signature. / Amiloride-sensitive sodium channel / Stimuli-sensing channels / negative regulation of neurotransmitter secretion / cellular response to pH / sodium ion transmembrane transport / response to acidic pH / associative learning / calcium ion transmembrane transport / regulation of membrane potential / protein homotrimerization / memory / synapse / integral component of plasma membrane / Golgi apparatus / identical protein binding / Acid-sensing ion channel 1|
Function and homology information
|Source||Gallus / bird / image: Gallus gallus|
|Method||single particle reconstruction, at 3.7 Å resolution|
|Authors||Yoder N / Yoshioka C|
|Citation||Journal: Nature / Year: 2018|
Title: Gating mechanisms of acid-sensing ion channels.
Authors: Nate Yoder / Craig Yoshioka / Eric Gouaux
Abstract: Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed ...Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive. Here we present structures of the high pH resting state of homotrimeric chicken (Gallus gallus) ASIC1a, determined by X-ray crystallography and single particle cryo-electron microscopy, and present a comprehensive molecular mechanism for proton-dependent gating in ASICs. In the resting state, the position of the thumb domain is further from the three-fold molecular axis, thereby expanding the 'acidic pocket' in comparison to the open and desensitized states. Activation therefore involves 'closure' of the thumb into the acidic pocket, expansion of the lower palm domain and an iris-like opening of the channel gate. Furthermore, we demonstrate how the β11-β12 linkers that demarcate the upper and lower palm domains serve as a molecular 'clutch', and undergo a simple rearrangement to permit rapid desensitization.
|Validation Report||PDB-ID: 6ave|
SummaryFull reportAbout validation report
|Date||Deposition: Sep 2, 2017 / Header (metadata) release: Dec 20, 2017 / Map release: Mar 21, 2018 / Last update: Mar 28, 2018|
Downloads & links
|File||emd_7009.map.gz (map file in CCP4 format, 32001 KB)|
|Projections & slices|
Images are generated by Spider package.
|Voxel size||X=Y=Z: 1.04 Å|
CCP4 map header:
-Entire Acid Sensing Ion Channel 1a
|Entire||Name: Acid Sensing Ion Channel 1a / Number of components: 3|
|Mass||Theoretical: 180.03144 kDa|
-Component #1: protein, Acid Sensing Ion Channel 1a
|Protein||Name: Acid Sensing Ion Channel 1a / Recombinant expression: No|
|Mass||Theoretical: 180.03144 kDa|
|Source||Species: Gallus / bird / image: Gallus gallus|
|Source (engineered)||Expression System: Homo sapiens / human /|
-Component #2: protein, Acid-sensing ion channel 1
|Protein||Name: Acid-sensing ion channel 1 / Recombinant expression: No|
|Mass||Theoretical: 60.080324 kDa|
|Source (engineered)||Expression System: Gallus gallus / bird / Chicken /|
-Component #3: ligand, N-ACETYL-D-GLUCOSAMINE
|Ligand||Name: N-ACETYL-D-GLUCOSAMINE / Number of Copies: 6 / Recombinant expression: No|
|Mass||Theoretical: 0.221208 kDa|
|Sample solution||Specimen conc.: 3.2 mg/ml / pH: 8|
|Support film||15 mA|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temperature: 291.15 K / Humidity: 1 %|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Imaging||Microscope: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 45 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 (4k x 4k)|
|Processing||Method: single particle reconstruction / Applied symmetry: C3 (3 fold cyclic) / Number of projections: 26117|
|3D reconstruction||Software: FREALIGN / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF|
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