The crystal structure of mouse VDAC1 at 2.3 A resolution reveals mechanistic insights into metabolite gating.
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.
Ujwal
Rachna
R
Department of Physiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Cascio
Duilio
D
Colletier
Jacques-Philippe
JP
Faham
Salem
S
Zhang
Jun
J
Toro
Ligia
L
Ping
Peipei
P
Abramson
Jeff
J
D000818:Animals; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D051379:Mice; D008958:Models, Molecular; D016062:Porosity; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012995:Solubility; D055672:Static Electricity; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry*
C494763:Vdac1 protein, mouse; D050995:Voltage-Dependent Anion Channel 1