3J2T

An improved model of the human apoptosome

「3IZA」から置き換えられました 「3IYT」から置き換えられました

3J2T の概要

• エントリーDOI: 10.2210/pdb3j2t/pdb
• EMDBエントリー: 5186
• 分子名称: Apoptotic protease-activating factor 1, Cytochrome c, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: apoptosis protease activating factor-1, apaf-1, cytochrome c, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 1097704.10

構造登録者

Yuan, S.,Topf, M.,Akey, C.W. (登録日: 2012-12-23, 公開日: 2013-04-10, 最終更新日: 2024-11-06)

主引用文献

Yuan, S.,Topf, M.,Reubold, T.F.,Eschenburg, S.,Akey, C.W.
Changes in apaf-1 conformation that drive apoptosome assembly.
Biochemistry, 52:2319-2327, 2013

PubMed Abstract: 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 ~9.5 Å resolution. The apoptosome model includes N-terminal domains of Apaf-1, cognate β-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 β-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 β-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.

PubMed: 23521171
DOI: 10.1021/bi301721g

実験手法

ELECTRON MICROSCOPY (9.5 Å)