Structural highlights
3x3f is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | |
| Gene: | DR5, KILLER, TNFRSF10B, TRAILR2, TRICK2, UNQ160/PRO186, ZTNFR9 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[TR10B_HUMAN] Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck.
Function
[TR10B_HUMAN] Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.[1]
Publication Abstract from PubMed
The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 A resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2.
TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.,Tamada T, Shinmi D, Ikeda M, Yonezawa Y, Kataoka S, Kuroki R, Mori E, Motoki K Sci Rep. 2015 Dec 17;5:17936. doi: 10.1038/srep17936. PMID:26672965[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004 Oct 29;279(44):45495-502. Epub 2004 Aug 18. PMID:15322075 doi:10.1074/jbc.M406933200
- ↑ Tamada T, Shinmi D, Ikeda M, Yonezawa Y, Kataoka S, Kuroki R, Mori E, Motoki K. TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2. Sci Rep. 2015 Dec 17;5:17936. doi: 10.1038/srep17936. PMID:26672965 doi:http://dx.doi.org/10.1038/srep17936
