3J9L

Structure of Dark apoptosome from Drosophila melanogaster

これはPDB形式変換不可エントリーです。

3J9L の概要

• エントリーDOI: 10.2210/pdb3j9l/pdb
• 関連するPDBエントリー: 3J9K
• EMDBエントリー: 2870 2871
• 分子名称: Apaf-1 related killer DARK, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE (2 entities in total)
• 機能のキーワード: programmed cell death, apoptosis
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 1812715.99

構造登録者

Pang, Y.,Bai, X.,Yan, C.,Hao, Q.,Chen, Z.,Wang, J.,Scheres, S.H.W.,Shi, Y. (登録日: 2015-02-04, 公開日: 2015-02-25, 最終更新日: 2024-02-21)

主引用文献

Pang, Y.,Bai, X.C.,Yan, C.,Hao, Q.,Chen, Z.,Wang, J.W.,Scheres, S.H.,Shi, Y.
Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila.
Genes Dev., 29:277-287, 2015

PubMed Abstract: Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome.

PubMed: 25644603
DOI: 10.1101/gad.255877.114

実験手法

ELECTRON MICROSCOPY (4 Å)