Structural highlights
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
