2na6

From Proteopedia

Transmembrane domain of mouse Fas/CD95 death receptor

PDB ID 2na6

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Structural highlights

2na6 is a 3 chain structure with sequence from Mus musculus. 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

TNR6_MOUSE Note=Defects in Fas are the cause of the lymphoproliferation phenotype (lpr). Lpr mice show lymphadenopathy and autoantibody production.

Function

TNR6_MOUSE Receptor for TNFSF6/FASLG. 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. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both (By similarity).

Publication Abstract from PubMed

Fas (CD95, Apo-1, or TNFRSF6) is a prototypical apoptosis-inducing death receptor in the tumor necrosis factor receptor (TNFR) superfamily. While the extracellular domains of TNFRs form trimeric complexes with their ligands and the intracellular domains engage in higher-order oligomerization, the role of the transmembrane (TM) domains is unknown. We determined the NMR structures of mouse and human Fas TM domains in bicelles that mimic lipid bilayers. Surprisingly, these domains use proline motifs to create optimal packing in homotrimer assembly distinct from classical trimeric coiled-coils in solution. Cancer-associated and structure-based mutations in Fas TM disrupt trimerization in vitro and reduce apoptosis induction in vivo, indicating the essential role of intramembrane trimerization in receptor activity. Our data suggest that the structures represent the signaling-active conformation of Fas TM, which appears to be different from the pre-ligand conformation. Analysis of other TNFR sequences suggests proline-containing sequences as common motifs for receptor TM trimerization.

Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor.,Fu Q, Fu TM, Cruz AC, Sengupta P, Thomas SK, Wang S, Siegel RM, Wu H, Chou JJ Mol Cell. 2016 Feb 18;61(4):602-13. doi: 10.1016/j.molcel.2016.01.009. Epub 2016 , Feb 4. PMID:26853147^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fu Q, Fu TM, Cruz AC, Sengupta P, Thomas SK, Wang S, Siegel RM, Wu H, Chou JJ. Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor. Mol Cell. 2016 Feb 18;61(4):602-13. doi: 10.1016/j.molcel.2016.01.009. Epub 2016 , Feb 4. PMID:26853147 doi:http://dx.doi.org/10.1016/j.molcel.2016.01.009