5WKU

Structure of an acid sensing ion channel in a resting state with barium

  • Classification: TRANSPORT PROTEIN
  • Organism(s): Gallus gallus
  • Expression System: Homo sapiens
  • Mutation(s): No 
  • Membrane Protein: Yes  OPMPDBTMMemProtMDmpstruc

  • Deposited: 2017-07-25 Released: 2018-03-14 
  • Deposition Author(s): Yoder, N., Gouaux, E.
  • Funding Organization(s): National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Gating mechanisms of acid-sensing ion channels.

Yoder, N.Yoshioka, C.Gouaux, E.

(2018) Nature 555: 397-401

  • DOI: https://doi.org/10.1038/nature25782
  • Primary Citation of Related Structures:  
    5WKU, 5WKV, 6AVE

  • PubMed 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 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.


  • Organizational Affiliation

    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acid-sensing ion channel 1A,
B [auth C],
C [auth B]
439Gallus gallusMutation(s): 0 
Gene Names: ASIC1ACCN2
Membrane Entity: Yes 
UniProt
Find proteins for Q1XA76 (Gallus gallus)
Explore Q1XA76 
Go to UniProtKB:  Q1XA76
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ1XA76
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A],
H [auth C],
I [auth C],
K [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
BA
Query on BA

Download Ideal Coordinates CCD File 
G [auth A]BARIUM ION
Ba
XDFCIPNJCBUZJN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
F [auth A],
J [auth C],
L [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.939α = 90
b = 130.408β = 90
c = 157.85γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United States5F31NS096782
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)United States5T32DK007680
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United States5R01NS038631

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-14
    Type: Initial release
  • Version 1.1: 2018-03-21
    Changes: Database references
  • Version 1.2: 2018-03-28
    Changes: Data collection, Database references
  • Version 1.3: 2019-02-20
    Changes: Author supporting evidence, Data collection
  • Version 1.4: 2019-12-18
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description, Structure summary