3jbt

Atomic structure of the Apaf-1 apoptosome

Loading... Status: waiting for Mol* initialization Structural highlights 3jbt is a 14 chain structure with sequence from Equus caballus and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DTP, HEM, MG Gene: APAF1, KIAA0413 (HUMAN) 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. [CYC_HORSE] 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 The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 A resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.,Zhou M, Li Y, Hu Q, Bai XC, Huang W, Yan C, Scheres SH, Shi Y Genes Dev. 2015 Nov 15;29(22):2349-61. doi: 10.1101/gad.272278.115. Epub 2015 Nov, 5. PMID:26543158 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Apoptotic protease-activating factor-1 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA