caspase-8 / death effector domain binding / syncytiotrophoblast cell differentiation involved in labyrinthine layer development / FasL/ CD95L signaling / TRAIL signaling / CD95 death-inducing signaling complex / ripoptosome / TRAIL-activated apoptotic signaling pathway / Defective RIPK1-mediated regulated necrosis / Apoptotic execution phase ...caspase-8 / death effector domain binding / syncytiotrophoblast cell differentiation involved in labyrinthine layer development / FasL/ CD95L signaling / TRAIL signaling / CD95 death-inducing signaling complex / ripoptosome / TRAIL-activated apoptotic signaling pathway / Defective RIPK1-mediated regulated necrosis / Apoptotic execution phase / Activation, myristolyation of BID and translocation to mitochondria / TRIF-mediated programmed cell death / TLR3-mediated TICAM1-dependent programmed cell death / Microbial modulation of RIPK1-mediated regulated necrosis / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / Caspase activation via Death Receptors in the presence of ligand / positive regulation of macrophage differentiation / self proteolysis / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / death-inducing signaling complex / CLEC7A/inflammasome pathway / natural killer cell activation / negative regulation of necroptotic process / activation of cysteine-type endopeptidase activity / regulation of tumor necrosis factor-mediated signaling pathway / tumor necrosis factor receptor binding / death receptor binding / cysteine-type endopeptidase activity involved in apoptotic process / TNFR1-induced proapoptotic signaling / execution phase of apoptosis / RIPK1-mediated regulated necrosis / detection of maltose stimulus / B cell activation / maltose transport complex / regulation of innate immune response / Apoptotic cleavage of cellular proteins / pyroptotic inflammatory response / carbohydrate transport / positive regulation of proteolysis / macrophage differentiation / protein maturation / cellular response to organic cyclic compound / carbohydrate transmembrane transporter activity / maltose binding / extrinsic apoptotic signaling pathway via death domain receptors / maltose transport / maltodextrin transmembrane transport / Caspase-mediated cleavage of cytoskeletal proteins / response to tumor necrosis factor / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / extrinsic apoptotic signaling pathway / negative regulation of canonical NF-kappaB signal transduction / cysteine-type peptidase activity / regulation of cytokine production / T cell activation / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / proteolysis involved in protein catabolic process / positive regulation of interleukin-1 beta production / Regulation of NF-kappa B signaling / apoptotic signaling pathway / Regulation of TNFR1 signaling / NOD1/2 Signaling Pathway / Regulation of necroptotic cell death / cellular response to mechanical stimulus / positive regulation of neuron apoptotic process / response to estradiol / lamellipodium / peptidase activity / heart development / cell body / outer membrane-bounded periplasmic space / scaffold protein binding / angiogenesis / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / mitochondrial outer membrane / response to lipopolysaccharide / periplasmic space / cytoskeleton / positive regulation of cell migration / positive regulation of apoptotic process / cysteine-type endopeptidase activity / apoptotic process / ubiquitin protein ligase binding / DNA damage response / protein-containing complex binding / protein-containing complex / mitochondrion / proteolysis / nucleoplasm / identical protein binding / membrane / cytoplasm / cytosol 類似検索 - 分子機能
Caspase-8 / Death effector domain / Death effector domain / Death effector domain (DED) profile. / Death effector domain / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. ...Caspase-8 / Death effector domain / Death effector domain / Death effector domain (DED) profile. / Death effector domain / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain / Caspase, interleukin-1 beta converting enzyme (ICE) homologues / Peptidase C14, p20 domain / Caspase family p20 domain profile. / : / Caspase domain / Caspase-like domain superfamily / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Death-like domain superfamily 類似検索 - ドメイン・相同性
: / Maltose/maltodextrin-binding periplasmic protein / Caspase-8 類似検索 - 構成要素
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)
DP1-HD087988
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R37-AI050872
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01-AI045937
米国
National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB)
R01-EB001567
米国
引用
ジャーナル: Mol Cell / 年: 2016 タイトル: Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex. 著者: Tian-Min Fu / Yang Li / Alvin Lu / Zongli Li / Parimala R Vajjhala / Anthony C Cruz / Devendra B Srivastava / Frank DiMaio / Pawel A Penczek / Richard M Siegel / Katryn J Stacey / Edward H Egelman / Hao Wu / 要旨: Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the ...Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the DISC and with ASC at the inflammasome through its tandem death effector domain (tDED), which is regulated by the tDED-containing cellular inhibitor cFLIP and the viral inhibitor MC159. Here we present the caspase-8 tDED filament structure determined by cryoelectron microscopy. Extensive assembly interfaces not predicted by the previously proposed linear DED chain model were uncovered, and were further confirmed by structure-based mutagenesis in filament formation in vitro and Fas-induced apoptosis and ASC-mediated caspase-8 recruitment in cells. Structurally, the two DEDs in caspase-8 use quasi-equivalent contacts to enable assembly. Using the tDED filament structure as a template, structural analyses reveal the interaction surfaces between FADD and caspase-8 and the distinct mechanisms of regulation by cFLIP and MC159 through comingling and capping, respectively.