Structural highlights
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.[1]
Publication Abstract from PubMed
The formation of death-inducing signaling complex (DISC) and death effector domain (DED) filament initiates extrinsic apoptosis. Recruitment and activation of procaspase-8 at the DISC are regulated by c-FLIP. The interaction between c-FLIP and procaspase-8 is mediated by their tandem DEDs (tDED). However, the structure of c-FLIP(tDED) and how c-FLIP interferes with procaspase-8 activation at the DISC remain elusive. Here, we solved the monomeric structure of c-FLIP(tDED) (F114G) at near physiological pH by solution nuclear magnetic resonance (NMR). Structural superimposition reveals c-FLIP(tDED) (F114G) adopts a structural topology similar to that of procaspase-8(tDED). Our results provide a structural basis for understanding how c-FLIP interacts with procaspase-8 and the molecular mechanisms of c-FLIP in regulating cell death.
Solution structure of c-FLIP death effector domains.,Bai ZQ, Ma X, Liu B, Huang T, Hu K Biochem Biophys Res Commun. 2022 Aug 30;617(Pt 2):1-6. doi:, 10.1016/j.bbrc.2022.05.086. Epub 2022 May 29. PMID:35688044[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Scaffidi C, Schmitz I, Krammer PH, Peter ME. The role of c-FLIP in modulation of CD95-induced apoptosis. J Biol Chem. 1999 Jan 15;274(3):1541-8. PMID:9880531
- ↑ Bai ZQ, Ma X, Liu B, Huang T, Hu K. Solution structure of c-FLIP death effector domains. Biochem Biophys Res Commun. 2022 Aug 30;617(Pt 2):1-6. doi:, 10.1016/j.bbrc.2022.05.086. Epub 2022 May 29. PMID:35688044 doi:https://dx.doi.org/10.1016/j.bbrc.2022.05.086
