The crystal structure of mouse VDAC1 at 2.3 Å resolution reveals mechanistic insights into metabolite gating

被引:444
作者
Ujwal, Rachna [1 ,2 ]
Cascio, Duilio [4 ]
Colletier, Jacques-Philippe [4 ]
Faham, Salem [1 ]
Zhang, Jun [1 ,2 ]
Toro, Ligia [3 ]
Ping, Peipei [1 ,2 ]
Abramson, Jeff [1 ]
机构
[1] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Cardiovasc Res Labs, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Div Mol Med, Dept Anesthesiol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Energy, Inst Genom & Prote, Los Angeles, CA 90095 USA
关键词
beta-barrel; mitochondria; outer membrane protein; ATP flux;
D O I
10.1073/pnas.0809634105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The voltage-dependent anion channel (VDAC) constitutes the major pathway for the entry and exit of metabolites across the outer membrane of the mitochondria and can serve as a scaffold for molecules that modulate the organelle. We report the crystal structure of a beta-barrel eukaryotic membrane protein, the murine VDAC1 (mVDAC1) at 2.3 angstrom resolution, revealing a high-resolution image of its architecture formed by 19 beta-strands. Unlike the recent NMR structure of human VDAC1, the position of the voltage-sensing N-terminal segment is clearly resolved. The a-helix of the N-terminal segment is oriented against the interior wall, causing a partial narrowing at the center of the pore. This segment is ideally positioned to regulate the conductance of ions and metabolites passing through the VDAC pore.
引用
收藏
页码:17742 / 17747
页数:6
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