1Z6T

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

1Z6T の概要

• エントリーDOI: 10.2210/pdb1z6t/pdb
• 分子名称: Apoptotic protease activating factor 1, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: apaf-1, caspase activation, adp, nucleotide binding, card, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O14727
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 273128.84

構造登録者

Riedl, S.J.,Li, W.,Chao, Y.,Schwarzenbacher, R.,Shi, Y. (登録日: 2005-03-23, 公開日: 2005-04-19, 最終更新日: 2024-02-14)

主引用文献

Riedl, S.J.,Li, W.,Chao, Y.,Schwarzenbacher, R.,Shi, Y.
Structure of the apoptotic protease-activating factor 1 bound to ADP
Nature, 434:926-933, 2005

PubMed Abstract: 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.

PubMed: 15829969
DOI: 10.1038/nature03465

実験手法

X-RAY DIFFRACTION (2.21 Å)