3RVY

Crystal structure of the NavAb voltage-gated sodium channel (Ile217Cys, 2.7 A)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.266 
  • R-Value Observed: 0.266 

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This is version 1.2 of the entry. See complete history


Literature

The crystal structure of a voltage-gated sodium channel.

Payandeh, J.Scheuer, T.Zheng, N.Catterall, W.A.

(2011) Nature 475: 353-358

  • DOI: https://doi.org/10.1038/nature10238
  • Primary Citation of Related Structures:  
    3RVY, 3RVZ, 3RW0

  • PubMed Abstract: 

    Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 Å resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, ∼4.6 Å wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na(+) selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.


  • Organizational Affiliation

    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ion transport protein
A, B
285Aliarcobacter butzleri RM4018Mutation(s): 1 
Gene Names: Abu_1752
Membrane Entity: Yes 
UniProt
Find proteins for A8EVM5 (Aliarcobacter butzleri (strain RM4018))
Explore A8EVM5 
Go to UniProtKB:  A8EVM5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA8EVM5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.266 
  • R-Value Observed: 0.266 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 125.594α = 90
b = 125.483β = 90
c = 192.297γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-07-13
    Type: Initial release
  • Version 1.1: 2011-07-27
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations