6BBF

The CRAC channel Orai in an open conformation; H206A gain-of-function mutation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 6.71 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.312 
  • R-Value Observed: 0.315 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structures reveal opening of the store-operated calcium channel Orai.

Hou, X.Burstein, S.R.Long, S.B.

(2018) Elife 7

  • DOI: https://doi.org/10.7554/eLife.36758
  • Primary Citation of Related Structures:  
    6BBF, 6BBG, 6BBH, 6BBI

  • PubMed Abstract: 

    The store-operated calcium (Ca 2+ ) channel Orai governs Ca 2+ influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to the depletion of Ca 2+ stored in the endoplasmic reticulum (ER). Loss- and gain-of-function mutants of Orai cause disease. Our previous work revealed the structure of Orai with a closed pore. Here, using a gain-of-function mutation that constitutively activates the channel, we present an X-ray structure of Drosophila melanogaster Orai in an open conformation. Well-defined electron density maps reveal that the pore is dramatically dilated on its cytosolic side in comparison to the slender closed pore. Cations and anions bind in different regions of the open pore, informing mechanisms for ion permeation and Ca 2+ selectivity. Opening of the pore requires the release of cytosolic latches. Together with additional X-ray structures of an unlatched-but-closed conformation, we propose a sequence for store-operated activation.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calcium release-activated calcium channel protein 1
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X
214Drosophila melanogasterMutation(s): 3 
Gene Names: olf186-FCRACM1olf186CG11430
Membrane Entity: Yes 
UniProt
Find proteins for Q9U6B8 (Drosophila melanogaster)
Explore Q9U6B8 
Go to UniProtKB:  Q9U6B8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9U6B8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 6.71 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.312 
  • R-Value Observed: 0.315 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 262.344α = 90
b = 262.344β = 90
c = 220.443γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM094273

Revision History  (Full details and data files)

  • Version 1.0: 2018-09-12
    Type: Initial release
  • Version 1.1: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.2: 2023-08-16
    Changes: Data collection, Database references, Other