4DW1

Crystal structure of the ATP-gated P2X4 ion channel in the ATP-bound, open state at 2.8 Angstroms


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Molecular mechanism of ATP binding and ion channel activation in P2X receptors.

Hattori, M.Gouaux, E.

(2012) Nature 485: 207-212

  • DOI: https://doi.org/10.1038/nature11010
  • Primary Citation of Related Structures:  
    4DW0, 4DW1

  • PubMed Abstract: 

    P2X receptors are trimeric ATP-activated ion channels permeable to Na+, K+ and Ca2+. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body β-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.


  • Organizational Affiliation

    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
P2X purinoceptor340Danio rerioMutation(s): 3 
Gene Names: p2rx4a
Membrane Entity: Yes 
UniProt
Find proteins for F8W463 (Danio rerio)
Explore F8W463 
Go to UniProtKB:  F8W463
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupF8W463
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
6N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42984ZU
GlyCosmos:  G42984ZU
GlyGen:  G42984ZU
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.791α = 90
b = 128.791β = 90
c = 252.074γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-25
    Type: Initial release
  • Version 1.1: 2012-05-02
    Changes: Database references
  • Version 1.2: 2013-01-09
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary