4J6G

CRYSTAL STRUCTURE OF LIGHT AND DcR3 COMPLEX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

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Literature

Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly.

Liu, W.Zhan, C.Cheng, H.Kumar, P.R.Bonanno, J.B.Nathenson, S.G.Almo, S.C.

(2014) Structure 22: 1252-1262

  • DOI: https://doi.org/10.1016/j.str.2014.06.013
  • Primary Citation of Related Structures:  
    4EN0, 4J6G, 4KG8, 4KGG, 4KGQ

  • PubMed Abstract: 

    LIGHT initiates intracellular signaling via engagement of the two TNF receptors, HVEM and LTβR. In humans, LIGHT is neutralized by DcR3, a unique soluble member of the TNFR superfamily, which tightly binds LIGHT and inhibits its interactions with HVEM and LTβR. DcR3 also neutralizes two other TNF ligands, FasL and TL1A. Due to its ability to neutralize three distinct different ligands, DcR3 contributes to a wide range of biological and pathological processes, including cancer and autoimmune diseases. However, the mechanisms that support the broad specificity of DcR3 remain to be fully defined. We report the structures of LIGHT and the LIGHT:DcR3 complex, which reveal the structural basis for the DcR3-mediated neutralization of LIGHT and afford insights into DcR3 function and binding promiscuity. Based on these structures, we designed LIGHT mutants with altered affinities for DcR3 and HVEM, which may represent mechanistically informative probe reagents.


  • Organizational Affiliation

    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor necrosis factor ligand superfamily member 14
A, B
165Homo sapiensMutation(s): 1 
Gene Names: TNFSF14HVEMLLIGHTUNQ391/PRO726
UniProt & NIH Common Fund Data Resources
Find proteins for O43557 (Homo sapiens)
Explore O43557 
Go to UniProtKB:  O43557
PHAROS:  O43557
GTEx:  ENSG00000125735 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43557
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor necrosis factor receptor superfamily member 6B
C, D
174Homo sapiensMutation(s): 0 
Gene Names: TNFRSF6BDCR3TR6UNQ186/PRO212
UniProt & NIH Common Fund Data Resources
Find proteins for O95407 (Homo sapiens)
Explore O95407 
Go to UniProtKB:  O95407
PHAROS:  O95407
GTEx:  ENSG00000243509 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95407
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 149.058α = 90
b = 149.058β = 90
c = 149.058γ = 90
Software Package:
Software NamePurpose
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-13
    Type: Initial release
  • Version 1.1: 2013-04-03
    Changes: Structure summary
  • Version 1.2: 2014-12-31
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-09-20
    Changes: Data collection, Database references, Refinement description, Structure summary