1z6t

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Revision as of 18:23, 12 November 2007

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spinqualitylabelsall models 1z6t, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of the apoptotic protease-activating factor 1 bound to ADP

Overview

Apoptosis is executed by caspases, which undergo proteolytic activation in, response to cell death stimuli. The apoptotic protease-activating factor 1, (Apaf-1) controls caspase activation downstream of mitochondria. During, apoptosis, Apaf-1 binds to cytochrome c and in the presence of ATP/dATP, forms an apoptosome, leading to the recruitment and activation of the, initiator caspase, caspase-9 (ref. 2). The mechanisms underlying Apaf-1, function are largely unknown. Here we report the 2.2-A crystal structure, of an ADP-bound, WD40-deleted Apaf-1, which reveals the molecular, mechanism by which Apaf-1 exists in an inactive state before ATP binding., The amino-terminal caspase recruitment domain packs against a, three-layered alpha/beta fold, a short helical motif and a winged-helix, domain, resulting in the burial of the caspase-9-binding interface. The, deeply buried ADP molecule serves as an organizing centre to strengthen, interactions between these four adjoining domains, thus locking Apaf-1 in, an inactive conformation. Apaf-1 binds to and hydrolyses ATP/dATP and, their analogues. The binding and hydrolysis of nucleotides seem to drive, conformational changes that are essential for the formation of the, apoptosome and the activation of caspase-9.

About this Structure

1Z6T is a Single protein structure of sequence from Homo sapiens with ADP as ligand. Full crystallographic information is available from OCA.

Reference

Structure of the apoptotic protease-activating factor 1 bound to ADP., Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y, Nature. 2005 Apr 14;434(7035):926-33. PMID:15829969

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