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J Biol Chem. 2012 Mar 30;287(14):11437-45. doi: 10.1074/jbc.M111.314229. Epub 2012 Jan 24.

Affixing N-terminal α-helix to the wall of the voltage-dependent anion channel does not prevent its voltage gating.

Author information

1
Program in Physical Biology, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

The voltage-dependent anion channel (VDAC) governs the free exchange of ions and metabolites between the mitochondria and the rest of the cell. The three-dimensional structure of VDAC1 reveals a channel formed by 19 β-strands and an N-terminal α-helix located near the midpoint of the pore. The position of this α-helix causes a narrowing of the cavity, but ample space for metabolite passage remains. The participation of the N-terminus of VDAC1 in the voltage-gating process has been well established, but the molecular mechanism continues to be debated; however, the majority of models entail large conformational changes of this N-terminal segment. Here we report that the pore-lining N-terminal α-helix does not undergo independent structural rearrangements during channel gating. We engineered a double Cys mutant in murine VDAC1 that cross-links the α-helix to the wall of the β-barrel pore and reconstituted the modified protein into planar lipid bilayers. The modified murine VDAC1 exhibited typical voltage gating. These results suggest that the N-terminal α-helix is located inside the pore of VDAC in the open state and remains associated with β-strand 11 of the pore wall during voltage gating.

PMID:
22275367
PMCID:
PMC3322836
DOI:
10.1074/jbc.M111.314229
[Indexed for MEDLINE]
Free PMC Article

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