Apaf-1-Caspase-9 holoenzyme with peripheral CARD ring
Sample
Complex: Apaf-1-Caspase-9 holoenzyme with refined peripheral CARD ring
Function / homology
Function and homology information
caspase-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / Formation of apoptosome / regulation of apoptotic DNA fragmentation / apoptosome / cytochrome complex / leukocyte apoptotic process / glial cell apoptotic process ...caspase-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / Formation of apoptosome / regulation of apoptotic DNA fragmentation / apoptosome / cytochrome complex / leukocyte apoptotic process / glial cell apoptotic process / cysteine-type endopeptidase activator activity / response to cobalt ion / response to anesthetic / Caspase activation via Dependence Receptors in the absence of ligand / Activation of caspases through apoptosome-mediated cleavage / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / fibroblast apoptotic process / AKT phosphorylates targets in the cytosol / mitochondrial electron transport, cytochrome c to oxygen / epithelial cell apoptotic process / platelet formation / cysteine-type endopeptidase activator activity involved in apoptotic process / mitochondrial electron transport, ubiquinol to cytochrome c / TP53 Regulates Transcription of Caspase Activators and Caspases / Constitutive Signaling by AKT1 E17K in Cancer / Transcriptional Regulation by E2F6 / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / signal transduction in response to DNA damage / forebrain development / cellular response to transforming growth factor beta stimulus / heat shock protein binding / cardiac muscle cell apoptotic process / response to nutrient / cellular response to dexamethasone stimulus / intrinsic apoptotic signaling pathway / protein maturation / enzyme activator activity / positive regulation of apoptotic signaling pathway / response to ischemia / kidney development / neural tube closure / apoptotic signaling pathway / NOD1/2 Signaling Pathway / protein processing / ADP binding / mitochondrial intermembrane space / SH3 domain binding / intrinsic apoptotic signaling pathway in response to DNA damage / cellular response to UV / positive regulation of neuron apoptotic process / nervous system development / response to estradiol / peptidase activity / secretory granule lumen / neuron apoptotic process / regulation of apoptotic process / response to lipopolysaccharide / ficolin-1-rich granule lumen / cell differentiation / electron transfer activity / response to hypoxia / positive regulation of apoptotic process / cysteine-type endopeptidase activity / nucleotide binding / apoptotic process / lipid binding / heme binding / DNA damage response / Neutrophil degranulation / protein kinase binding / protein-containing complex / mitochondrion / proteolysis / extracellular exosome / extracellular region / ATP binding / metal ion binding / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function
Journal: Proc Natl Acad Sci U S A / Year: 2017 Title: Mechanistic insights into caspase-9 activation by the structure of the apoptosome holoenzyme. Authors: Yini Li / Mengying Zhou / Qi Hu / Xiao-Chen Bai / Weiyun Huang / Sjors H W Scheres / Yigong Shi / Abstract: Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is ...Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme. The molecular mechanism of caspase-9 activation remains largely enigmatic. Here, we report the cryoelectron microscopy (cryo-EM) structure of an apoptotic holoenzyme and structure-guided biochemical analyses. The caspase recruitment domains (CARDs) of Apaf-1 and caspase-9 assemble in two different ways: a 4:4 complex docks onto the central hub of the apoptosome, and a 2:1 complex binds the periphery of the central hub. The interface between the CARD complex and the central hub is required for caspase-9 activation within the holoenzyme. Unexpectedly, the CARD of free caspase-9 strongly inhibits its proteolytic activity. These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain.
History
Deposition
Dec 24, 2016
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Header (metadata) release
Jan 18, 2017
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Map release
Mar 1, 2017
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Update
Mar 1, 2017
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Current status
Mar 1, 2017
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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