| Structural highlights
4kgg is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | BMA, MG, MAN, NAG |
| Related: | 4en0, 3k51, 3mi8, 3mhd, 4j6g |
| Gene: | TNFRSF6B, DCR3, TR6, UNQ186/PRO212 (HUMAN), TNFSF14, HVEML, LIGHT, UNQ391/PRO726 (HUMAN) |
| 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] [TNF14_HUMAN] Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus.
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.
See Also
References
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1016/j.str.2014.06.013
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