6G9O

Structure of full-length homomeric mLRRC8A volume-regulated anion channel at 4.25 A resolution


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.25 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of a volume-regulated anion channel of the LRRC8 family.

Deneka, D.Sawicka, M.Lam, A.K.M.Paulino, C.Dutzler, R.

(2018) Nature 558: 254-259

  • DOI: https://doi.org/10.1038/s41586-018-0134-y
  • Primary Citation of Related Structures:  
    6FNW, 6G8Z, 6G9L, 6G9O

  • PubMed Abstract: 

    Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.


  • Organizational Affiliation

    Department of Biochemistry, University of Zurich, Zurich, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Volume-regulated anion channel subunit LRRC8A
A, B, C, D, E
A, B, C, D, E, F
810Mus musculusMutation(s): 0 
Gene Names: Lrrc8aLrrc8
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q80WG5 (Mus musculus)
Explore Q80WG5 
Go to UniProtKB:  Q80WG5
IMPC:  MGI:2652847
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ80WG5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.25 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION
MODEL REFINEMENTPHENIX
MODEL REFINEMENTREFMAC

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland31003A_163421

Revision History  (Full details and data files)

  • Version 1.0: 2018-05-16
    Type: Initial release
  • Version 1.1: 2018-05-30
    Changes: Data collection, Database references
  • Version 1.2: 2018-06-27
    Changes: Data collection, Database references
  • Version 1.3: 2019-12-11
    Changes: Other