5SVK

Crystal structure of the ATP-gated human P2X3 ion channel in the ATP-bound, open state


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.77 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

X-ray structures define human P2X3 receptor gating cycle and antagonist action.

Mansoor, S.E.Lu, W.Oosterheert, W.Shekhar, M.Tajkhorshid, E.Gouaux, E.

(2016) Nature 538: 66-71

  • DOI: https://doi.org/10.1038/nature19367
  • Primary Citation of Related Structures:  
    5SVJ, 5SVK, 5SVL, 5SVM, 5SVP, 5SVQ, 5SVR, 5SVS, 5SVT

  • PubMed Abstract: 

    P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X 3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the 'cytoplasmic cap', which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
P2X purinoceptor 3
A, B
363Homo sapiensMutation(s): 3 
Gene Names: P2RX3
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P56373 (Homo sapiens)
Explore P56373 
Go to UniProtKB:  P56373
PHAROS:  P56373
GTEx:  ENSG00000109991 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56373
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose
C, D, E, F
2N/A
Glycosylation Resources
GlyTouCan:  G07411ON
GlyCosmos:  G07411ON
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
G [auth A],
N [auth B]
ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
J [auth A]
K [auth A]
O [auth B]
H [auth A],
I [auth A],
J [auth A],
K [auth A],
O [auth B],
P [auth B],
Q [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
MHA
Query on MHA

Download Ideal Coordinates CCD File 
M [auth A](CARBAMOYLMETHYL-CARBOXYMETHYL-AMINO)-ACETIC ACID
C6 H10 N2 O5
QZTKDVCDBIDYMD-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
L [auth A],
R [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ATP BindingDB:  5SVK EC50: 340 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.77 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.202 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 173.15α = 90
b = 173.15β = 90
c = 173.15γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-28
    Type: Initial release
  • Version 1.1: 2016-10-19
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary