4kgq

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Crystal structure of a human light loop mutant in complex with dcr3

Structural highlights

4kgq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.27Å
Ligands:BMA, MAN, MG, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TNF6B_HUMAN Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.[1]

Publication Abstract from PubMed

LIGHT initiates intracellular signaling via engagement of the two TNF receptors, HVEM and LTbetaR. 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 LTbetaR. 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.

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 PR, Bonanno JB, Nathenson SG, Almo SC Structure. 2014 Sep 2;22(9):1252-62. doi: 10.1016/j.str.2014.06.013. Epub 2014, Jul 31. PMID:25087510[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
6 reviews cite this structure
The TNF Receptor Superfamily in Co-stimulating and Co-inhibitory Responses.
Ward-Kavanagh et al. (2016)
5 more
17 other articles
No citations found

See Also

References

  1. ↑ Zhan C, Patskovsky Y, Yan Q, Li Z, Ramagopal U, Cheng H, Brenowitz M, Hui X, Nathenson SG, Almo SC. Decoy Strategies: The Structure of TL1A:DcR3 Complex. Structure. 2011 Feb 9;19(2):162-71. PMID:21300286 doi:10.1016/j.str.2010.12.004
  2. ↑ Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC. Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly. Structure. 2014 Sep 2;22(9):1252-62. doi: 10.1016/j.str.2014.06.013. Epub 2014, Jul 31. PMID:25087510 doi:http://dx.doi.org/10.1016/j.str.2014.06.013

Contents


PDB ID 4kgq

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