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

Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17742-7. doi: 10.1073/pnas.0809634105. Epub 2008 Nov 6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / chemistry*

Substances

  • Vdac1 protein, mouse
  • Voltage-Dependent Anion Channel 1

Associated data

  • PDB/3EMN