1NW9

STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3

1NW9 の概要

• エントリーDOI: 10.2210/pdb1nw9/pdb
• 分子名称: Baculoviral IAP repeat-containing protein 4, caspase 9, apoptosis-related cysteine protease, ZINC ION (3 entities in total)
• 機能のキーワード: caspase-9, xiap, caspase inhibition, caspase activation, dimerization, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41866.65

構造登録者

Shiozaki, E.N.,Chai, J.,Rigotti, D.J.,Riedl, S.J.,Li, P.,Srinivasula, S.M.,Alnemri, E.S.,Fairman, R.,Shi, Y. (登録日: 2003-02-05, 公開日: 2003-03-25, 最終更新日: 2024-02-14)

主引用文献

Shiozaki, E.N.,Chai, J.,Rigotti, D.J.,Riedl, S.J.,Li, P.,Srinivasula, S.M.,Alnemri, E.S.,Fairman, R.,Shi, Y.
Mechanism of XIAP-Mediated Inhibition of Caspase-9
Mol.Cell, 11:519-527, 2003

PubMed Abstract: The inhibitor of apoptosis (IAP) proteins potently inhibit the catalytic activity of caspases. While profound insight into the inhibition of the effector caspases has been gained in recent years, the mechanism of how the initiator caspase-9 is regulated by IAPs remains enigmatic. This paper reports the crystal structure of caspase-9 in an inhibitory complex with the third baculoviral IAP repeat (BIR3) of XIAP at 2.4 A resolution. The structure reveals that the BIR3 domain forms a heterodimer with a caspase-9 monomer. Strikingly, the surface of caspase-9 that interacts with BIR3 also mediates its homodimerization. We demonstrate that monomeric caspase-9 is catalytically inactive due to the absence of a supporting sequence element that could be provided by homodimerization. Thus, XIAP sequesters caspase-9 in a monomeric state, which serves to prevent catalytic activity. These studies, in conjunction with other observations, define a unified mechanism for the activation of all caspases.

PubMed: 12620238
DOI: 10.1016/S1097-2765(03)00054-6

実験手法

X-RAY DIFFRACTION (2.4 Å)