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

Publication Type:

Journal Article

Authors:

Ujwal, Rachna; Cascio, Duilio; Colletier, Jacques-Philippe; Faham, Salem; Zhang, Jun; Toro, Ligia; Ping, Peipei; Abramson, Jeff

Source:

Proc Natl Acad Sci U S A, Volume 105, Issue 46, p.17742-7 (2008)

Keywords:

Animals, Crystallography, X-Ray, Ion Channel Gating, Mice, Models, Molecular, Porosity, Protein Structure, Secondary, Protein Structure, Tertiary, Solubility, Static Electricity, Voltage-Dependent Anion Channel 1

Abstract:

<p>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 A 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 alpha-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.</p>