| Structural highlights
3mi8 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 2qe3, 3k51, 3mhd |
| Gene: | TL1, TNFSF15, VEGI (HUMAN), DcR3, TNFRSF6B (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[TNF15_HUMAN] Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.[1] [2] [3] [4] [TNF6B_HUMAN] Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.[5]
Publication Abstract from PubMed
Decoy Receptor 3 (DcR3), a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, neutralizes three different TNF ligands: FasL, LIGHT, and TL1A. Each of these ligands engages unique signaling receptors which direct distinct and critical immune responses. We report the crystal structures of the unliganded DcR3 ectodomain and its complex with TL1A, as well as complementary mutagenesis and biochemical studies. These analyses demonstrate that DcR3 interacts with invariant backbone and side-chain atoms in the membrane-proximal half of TL1A which supports recognition of its three distinct TNF ligands. Additional features serve as antideterminants that preclude interaction with other members of the TNF superfamily. This mode of interaction is unique among characterized TNF:TNFR family members and provides a mechanistic basis for the broadened specificity required to support the decoy function of DcR3, as well as for the rational manipulation of specificity and affinity of DcR3 and its ligands.
Decoy Strategies: The Structure of TL1A:DcR3 Complex.,Zhan C, Patskovsky Y, Yan Q, Li Z, Ramagopal U, Cheng H, Brenowitz M, Hui X, Nathenson SG, Almo SC Structure. 2011 Feb 9;19(2):162-71. PMID:21300286[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhai Y, Ni J, Jiang GW, Lu J, Xing L, Lincoln C, Carter KC, Janat F, Kozak D, Xu S, Rojas L, Aggarwal BB, Ruben S, Li LY, Gentz R, Yu GL. VEGI, a novel cytokine of the tumor necrosis factor family, is an angiogenesis inhibitor that suppresses the growth of colon carcinomas in vivo. FASEB J. 1999 Jan;13(1):181-9. PMID:9872942
- ↑ Chew LJ, Pan H, Yu J, Tian S, Huang WQ, Zhang JY, Pang S, Li LY. A novel secreted splice variant of vascular endothelial cell growth inhibitor. FASEB J. 2002 May;16(7):742-4. Epub 2002 Mar 26. PMID:11923219 doi:10.1096/fj.01-0757fje
- ↑ Migone TS, Zhang J, Luo X, Zhuang L, Chen C, Hu B, Hong JS, Perry JW, Chen SF, Zhou JX, Cho YH, Ullrich S, Kanakaraj P, Carrell J, Boyd E, Olsen HS, Hu G, Pukac L, Liu D, Ni J, Kim S, Gentz R, Feng P, Moore PA, Ruben SM, Wei P. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 2002 Mar;16(3):479-92. PMID:11911831
- ↑ Haridas V, Shrivastava A, Su J, Yu GL, Ni J, Liu D, Chen SF, Ni Y, Ruben SM, Gentz R, Aggarwal BB. VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth. Oncogene. 1999 Nov 11;18(47):6496-504. PMID:10597252 doi:10.1038/sj.onc.1203059
- ↑ 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
- ↑ 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
|
