+Open data
-Basic information
Entry | Database: PDB / ID: 8yd8 | ||||||
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Title | Structure of FADD/Caspase-8/cFLIP death effector domain assembly | ||||||
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Keywords | APOPTOSIS / FADD / Caspase-8 / cFLIP / death effector domain | ||||||
Function / homology | Function and homology information positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation / negative regulation of myoblast fusion / negative regulation of activation-induced cell death of T cells / skeletal myofibril assembly / caspase-8 / death effector domain binding / syncytiotrophoblast cell differentiation involved in labyrinthine layer development / FasL/ CD95L signaling / skeletal muscle atrophy / tumor necrosis factor receptor superfamily binding ...positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation / negative regulation of myoblast fusion / negative regulation of activation-induced cell death of T cells / skeletal myofibril assembly / caspase-8 / death effector domain binding / syncytiotrophoblast cell differentiation involved in labyrinthine layer development / FasL/ CD95L signaling / skeletal muscle atrophy / tumor necrosis factor receptor superfamily binding / TRAIL signaling / CD95 death-inducing signaling complex / regulation of skeletal muscle satellite cell proliferation / ripoptosome / TRAIL-activated apoptotic signaling pathway / death-inducing signaling complex assembly / 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 / regulation of necroptotic process / positive regulation of adaptive immune response / Caspase activation via Death Receptors in the presence of ligand / positive regulation of extracellular matrix organization / skeletal muscle tissue regeneration / positive regulation of glomerular mesangial cell proliferation / positive regulation of macrophage differentiation / necroptotic signaling pathway / caspase binding / 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 / negative regulation of hepatocyte apoptotic process / CLEC7A/inflammasome pathway / natural killer cell activation / receptor serine/threonine kinase binding / negative regulation of necroptotic process / activation of cysteine-type endopeptidase activity / cysteine-type endopeptidase activity involved in execution phase of apoptosis / positive regulation of innate immune response / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of type I interferon-mediated signaling pathway / tumor necrosis factor receptor binding / death receptor binding / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of hepatocyte proliferation / cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of cellular response to transforming growth factor beta stimulus / motor neuron apoptotic process / TNFR1-induced proapoptotic signaling / execution phase of apoptosis / RIPK1-mediated regulated necrosis / negative regulation of cardiac muscle cell apoptotic process / response to testosterone / B cell activation / positive regulation of activated T cell proliferation / regulation of innate immune response / Apoptotic cleavage of cellular proteins / pyroptotic inflammatory response / positive regulation of execution phase of apoptosis / T cell homeostasis / positive regulation of proteolysis / behavioral response to cocaine / macrophage differentiation / protein maturation / cellular response to organic cyclic compound / extrinsic apoptotic signaling pathway via death domain receptors / cellular response to nitric oxide / Caspase-mediated cleavage of cytoskeletal proteins / response to tumor necrosis factor / lymph node development / signaling adaptor activity / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of canonical NF-kappaB signal transduction / skeletal muscle tissue development / cysteine-type peptidase activity / keratinocyte differentiation / extrinsic apoptotic signaling pathway in absence of ligand / enzyme activator activity / spleen development / cellular response to epidermal growth factor stimulus / regulation of cytokine production / T cell activation / erythrocyte differentiation / cellular response to dexamethasone stimulus / thymus development / proteolysis involved in protein catabolic process / positive regulation of interleukin-1 beta production / kidney development / Regulation of NF-kappa B signaling / cellular response to estradiol stimulus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.11 Å | ||||||
Authors | Lin, S.-C. / Yang, C.-Y. | ||||||
Funding support | Taiwan, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis. Authors: Chao-Yu Yang / Chia-I Lien / Yi-Chun Tseng / Yi-Fan Tu / Arkadiusz W Kulczyk / Yen-Chen Lu / Yin-Ting Wang / Tsung-Wei Su / Li-Chung Hsu / Yu-Chih Lo / Su-Chang Lin / Abstract: Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling ...Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions. These structures illustrate how FADD and cFLIP orchestrate the assembly of caspase-8-containing complexes and offer mechanistic explanations for their role in promoting or inhibiting apoptotic and necroptotic signaling. A helical procaspase-8-cFLIP hetero-double layer in the complex appears to promote limited caspase-8 activation for cell survival. Our structure-guided mutagenesis supports the role of the triple-FADD complex in caspase-8 activation and in regulating receptor-interacting protein kinase 1 (RIPK1). These results propose a unified mechanism for DED assembly and procaspase-8 activation in the regulation of apoptotic and necroptotic signaling across various cellular pathways involved in development, innate immunity, and disease. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
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PDBx/mmCIF format | 8yd8.cif.gz | 424.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8yd8.ent.gz | 280.6 KB | Display | PDB format |
PDBx/mmJSON format | 8yd8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8yd8_validation.pdf.gz | 491.2 KB | Display | wwPDB validaton report |
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Full document | 8yd8_full_validation.pdf.gz | 504.6 KB | Display | |
Data in XML | 8yd8_validation.xml.gz | 53.7 KB | Display | |
Data in CIF | 8yd8_validation.cif.gz | 72.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yd/8yd8 ftp://data.pdbj.org/pub/pdb/validation_reports/yd/8yd8 | HTTPS FTP |
-Related structure data
Related structure data | 8ybxC 8yd7C C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
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