3j2t

An improved model of the human apoptosome

Loading... Status: waiting for Mol* initialization Structural highlights 3j2t is a 14 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 9.5Å Ligands: ATP, HEM 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. Publication Abstract from PubMed Apoptosome assembly is highly regulated in the intrinsic cell death pathway. To better understand this step, we created an improved model of the human apoptosome using a crystal structure of full length Apaf-1 and a single particle, electron density map at approximately 9.5 A resolution. The apoptosome model includes N-terminal domains of Apaf-1, cognate beta-propellers, and cytochrome c. A direct comparison of Apaf-1 in the apoptosome and as a monomer reveals conformational changes that occur during the first two steps of assembly. This includes an induced-fit mechanism for cytochrome c binding to regulatory beta-propellers, which is dependent on shape and charge complementarity, and a large rotation of the nucleotide binding module during nucleotide exchange. These linked conformational changes create an extended Apaf-1 monomer and drive apoptosome assembly. Moreover, the N-terminal CARD in the inactive Apaf-1 monomer is not shielded from other proteins by beta-propellers. Hence, the Apaf-1 CARD may be free to interact with a procaspase-9 CARD either before or during apoptosome assembly. Irrespective of the timing, the end product of assembly is a holo-apoptosome with an acentric CARD-CARD disk and tethered pc-9 catalytic domains. Subsequent activation of pc-9 leads to a proteolytic cascade and cell death. Changes in apaf-1 conformation that drive apoptosome assembly.,Yuan S, Topf M, Reubold TF, Eschenburg S, Akey CW Biochemistry. 2013 Apr 2;52(13):2319-27. doi: 10.1021/bi301721g. Epub 2013 Mar, 22. PMID:23521171 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Apoptotic protease-activating factor-1 3D structures Cytochrome C 3D structures

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