4O6A

Mouse cyclic GMP-AMP synthase (cGAS) in complex with DNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.187 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop.

Zhang, X.Wu, J.Du, F.Xu, H.Sun, L.Chen, Z.Brautigam, C.A.Zhang, X.Chen, Z.J.

(2014) Cell Rep 6: 421-430

  • DOI: https://doi.org/10.1016/j.celrep.2014.01.003
  • Primary Citation of Related Structures:  
    4O67, 4O68, 4O69, 4O6A

  • PubMed Abstract: 

    The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.


  • Organizational Affiliation

    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Electronic address: [email protected].


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclic GMP-AMP synthaseA,
D [auth B]
362Mus musculusMutation(s): 0 
Gene Names: Mb21d1
EC: 2.7.7.86
UniProt & NIH Common Fund Data Resources
Find proteins for Q8C6L5 (Mus musculus)
Explore Q8C6L5 
Go to UniProtKB:  Q8C6L5
IMPC:  MGI:2442261
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8C6L5
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA1B [auth D],
E [auth C]
17N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA2C [auth E],
F
17N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.187 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 183.711α = 90
b = 96.33β = 98.28
c = 75.989γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASESphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-05
    Type: Initial release
  • Version 1.1: 2014-03-05
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations