期刊
MOLECULAR CELL
卷 56, 期 4, 页码 496-505出版社
CELL PRESS
DOI: 10.1016/j.molcel.2014.09.022
关键词
-
资金
- ETH Zurich
- Max Planck Society
- German Cancer Research Center
- German Ministry for Education and Research (BMBF) [0312040]
- DFG [FOR2036]
- SNF [200020_144441]
- [ERC-2012-StG_20111109]
- Swiss National Science Foundation (SNF) [200020_144441] Funding Source: Swiss National Science Foundation (SNF)
Bax plays a central role in the mitochondrial pathway of apoptosis. Upon activation, cytosolic Bax monomers oligomerize on the surface of mitochondria and change conformation concertedly to punch holes into the outer membrane. The subsequent release of cytochrome c initiates cell death. However, the structure of membrane-inserted Bax and its mechanism of action remain largely unknown. Here, we propose a 3D model of active Bax at the membrane based on double electron-electron resonance (DEER) spectroscopy in liposomes and isolated mitochondria. We show that active Bax is organized at the membrane as assemblies of dimers. In addition to a stable dimerization domain, each monomer contains a more flexible piercing domain involved in interdimer interactions and pore formation. The most important structural change during Bax activation is the opening of the hairpin formed by helices 5 and 6, which adopts a clamp-like conformation central to the mechanism of mitochondrial permeabilization.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据