5BQX

Crystal structure of human STING in complex with 3'2'-cGAMP

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli
  • Mutation(s): No 

  • Deposited: 2015-05-29 Released: 2015-06-24 
  • Deposition Author(s): Wu, J., Zhang, X., Chen, Z.J., Chen, C.
  • Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING.

Shi, H.Wu, J.Chen, Z.J.Chen, C.

(2015) Proc Natl Acad Sci U S A 112: 8947-8952

  • DOI: https://doi.org/10.1073/pnas.1507317112
  • Primary Citation of Related Structures:  
    5BQX

  • PubMed Abstract: 

    Cyclic GMP-AMP containing a unique combination of mixed phosphodiester linkages (2'3'-cGAMP) is an endogenous second messenger molecule that activates the type-I IFN pathway upon binding to the homodimer of the adaptor protein STING on the surface of endoplasmic reticulum membrane. However, the preferential binding of the asymmetric ligand 2'3'-cGAMP to the symmetric dimer of STING represents a physicochemical enigma. Here we show that 2'3'-cGAMP, but not its linkage isomers, adopts an organized free-ligand conformation that resembles the STING-bound conformation and pays low entropy and enthalpy costs in converting into the active conformation. Our results demonstrate that analyses of free-ligand conformations can be as important as analyses of protein conformations in understanding protein-ligand interactions.


  • Organizational Affiliation

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Stimulator of interferon genes protein242Homo sapiensMutation(s): 0 
Gene Names: TMEM173ERISMITASTING
UniProt & NIH Common Fund Data Resources
Find proteins for Q86WV6 (Homo sapiens)
Explore Q86WV6 
Go to UniProtKB:  Q86WV6
PHAROS:  Q86WV6
GTEx:  ENSG00000184584 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ86WV6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4UR
Query on 4UR

Download Ideal Coordinates CCD File 
B [auth A]3'2'-cGAMP
C20 H24 N10 O13 P2
FAFONCPHZLORMH-INFSMZHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.191 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.061α = 90
b = 111.061β = 90
c = 35.889γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesRO1-GM-079554
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesRO1-AI-093967

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-24
    Type: Initial release
  • Version 1.1: 2015-07-22
    Changes: Database references
  • Version 1.2: 2015-08-05
    Changes: Database references
  • Version 1.3: 2017-09-06
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.5: 2024-03-06
    Changes: Data collection, Database references