2FP3

Crystal structure of the Drosophila initiator caspase Dronc

2FP3 の概要

• エントリーDOI: 10.2210/pdb2fp3/pdb
• 分子名称: Caspase Nc (2 entities in total)
• 機能のキーワード: caspase, apoptosis, initiator caspase activation, dimerization, active site conformation, hydrolysis-apoptosis complex, hydrolysis/apoptosis
• 由来する生物種: Drosophila melanogaster (fruit fly)
• 細胞内の位置: Cytoplasm (By similarity): Q9XYF4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35609.32

構造登録者

Yan, N.,Gu, L.,Shi, Y. (登録日: 2006-01-15, 公開日: 2006-01-31, 最終更新日: 2024-02-14)

主引用文献

Yan, N.,Huh, J.R.,Schirf, V.,Demeler, B.,Hay, B.A.,Shi, Y.
Structure and activation mechanism of the Drosophila initiator caspase dronc
J.Biol.Chem., 281:8667-8674, 2006

PubMed Abstract: Activation of an initiator caspase is essential to the execution of apoptosis. The molecular mechanisms by which initiator caspases are activated remain poorly understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an important initiator caspase in Drosophila, results in a drastic enhancement of its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the autocatalytic cleavage in Dronc induces its stable dimerization, which presumably allows the two adjacent monomers to mutually stabilize their active sites, leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 A resolution, reveals an unproductive conformation at the active site, which is consistent with the observation that the zymogen remains catalytically inactive. This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases.

PubMed: 16446367
DOI: 10.1074/jbc.M513232200

実験手法

X-RAY DIFFRACTION (2.5 Å)