3h13 | pdb_00003h13

c-FLIPL protease-like domain

spinqualitylabelsall models 3h13, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3h13 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3h11 Gene: CFLAR, CASH, CASP8AP1, CLARP, MRIT (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CFLAR_HUMAN] Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Cellular FLICE-inhibitory protein (c-FLIP(L)) is a key regulator of the extrinsic cell death pathway. Although widely regarded as an inhibitor of initiator caspase activation and cell death, c-FLIP(L) is also capable of enhancing procaspase-8 activation through heterodimerization of their respective protease domains. However, the underlying mechanism of this activation process remains enigmatic. Here, we demonstrate that cleavage of the intersubunit linker of c-FLIP(L) by procaspase-8 potentiates the activation process by enhancing heterodimerization between the two proteins and vastly improving the proteolytic activity of unprocessed caspase-(C)8. The crystal structures of the protease-like domain of c-FLIP(L) alone and in complex with zymogen C8 identify the unique determinants that favor heterodimerization over procaspase-8 homodimerization, and induce the latent active site of zymogen C8 into a productive conformation. Together, these findings provide molecular insights into a key aspect of c-FLIP(L) function that modulates procaspase-8 activation to elicit diverse responses in different cellular contexts. Mechanism of procaspase-8 activation by c-FLIPL.,Yu JW, Jeffrey PD, Shi Y Proc Natl Acad Sci U S A. 2009 May 4. PMID:19416807 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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