|Entry||Database: PDB / ID: 6ave|
|Title||Structure of an acid sensing ion channel in a resting state at high pH|
|Components||Acid-sensing ion channel 1|
|Keywords||TRANSPORT PROTEIN / Ion channel / ASIC / ASIC1a / Sodium channel / MEMBRANE PROTEIN|
|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
|Specimen source||Gallus gallus / bird / Chicken /|
|Method||Electron microscopy (3.7 Å resolution / Particle / Single particle) / Transmission electron microscopy|
|Authors||Yoder, N. / Yoshioka, C. / Gouaux, E.|
|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.
SummaryFull reportAbout validation report
|Date||Deposition: Sep 2, 2017 / Release: Mar 21, 2018|
Downloads & links
A: Acid-sensing ion channel 1
B: Acid-sensing ion channel 1
C: Acid-sensing ion channel 1
Mass: 60080.324 Da / Num. of mol.: 3 / Source: (gene. exp.) Gallus gallus / bird / Chicken / / Gene: ASIC1, ACCN2 / Production host: Homo sapiens / References: UniProt:Q1XA76
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: SINGLE PARTICLE|
|Component||Name: Acid Sensing Ion Channel 1a / Type: COMPLEX / Entity ID: 1 / Source: RECOMBINANT|
|Molecular weight||Value: 0.18003144 deg. / Units: MEGADALTONS / Experimental value: NO|
|Source (natural)||Organism: Gallus|
|Source (recombinant)||Organism: Homo sapiens|
|Buffer solution||pH: 8|
|Specimen||Conc.: 3.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Details: 15 mA / Grid material: GOLD / Grid mesh size: 300 / Grid type: Quantifoil|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291.15 kelvins|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELD|
|Image recording||Average exposure time: 10 sec. / Electron dose: 45 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number of grids imaged: 1|
|Image scans||Movie frames/image: 100|
|Software||Name: PHENIX / Version: dev_2597: / Classification: refinement|
|CTF correction||Type: NONE|
|Symmetry||Point symmetry: C3|
|3D reconstruction||Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 26117 / Number of class averages: 1 / Symmetry type: POINT|
|Atomic model building||Ref space: REAL|
|Refine LS restraints|
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