6nhy

Structure of the transmembrane domain of the Death Receptor 5 mutant (G217Y) - Trimer Only

spinqualitylabelsall models 6nhy Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nhy is a 3 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. 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. Publication Abstract from PubMed Receptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the receptor directly assembles a higher-order structure to drive signaling and that this structure is inhibited by the unliganded ectodomain. Nuclear magnetic resonance structure of the TMH in bicelles shows distinct trimerization and dimerization faces, allowing formation of dimer-trimer interaction networks. Single-TMH mutations that disrupt either trimerization or dimerization abolish ligand-induced receptor activation. Surprisingly, proteolytic removal of the DR5 ectodomain can fully activate downstream signaling in the absence of ligand. Our data suggest a receptor activation mechanism in which binding of ligand or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling. Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling.,Pan L, Fu TM, Zhao W, Zhao L, Chen W, Qiu C, Liu W, Liu Z, Piai A, Fu Q, Chen S, Wu H, Chou JJ Cell. 2019 Mar 7;176(6):1477-1489.e14. doi: 10.1016/j.cell.2019.02.001. Epub 2019, Feb 28. PMID:30827683 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also TRAIL Tumor necrosis factor receptor 3D structures

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