5juy

Active human apoptosome with procaspase-9

spinqualitylabelsall models 5juy, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5juy is a 18 chain structure with sequence from Bos taurus and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DTP, HEC Gene: APAF1, KIAA0413 (HUMAN), CASP9, MCH6 (HUMAN) Activity: Caspase-9, with EC number 3.4.22.62 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [APAF_HUMAN] Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis. [CASP9_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. [CYC_BOVIN] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity). Publication Abstract from PubMed In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. A near atomic structure of the active human apoptosome.,Cheng TC, Hong C, Akey IV, Yuan S, Akey CW Elife. 2016 Oct 4;5. pii: e17755. doi: 10.7554/eLife.17755. PMID:27697150 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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