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Affixing N-terminal α-Helix to the Wall of the Voltage-dependent Anion Channel Does Not Prevent Its Voltage Gating
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 14, 11437-11445 p.Article in journal (Refereed) Published
Abstract [en]

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 beta-strands and an N-terminal alpha-helix located near the midpoint of the pore. The position of this alpha-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 alpha-helix does not undergo independent structural rearrangements during channel gating. We engineered a double Cys mutant in murine VDAC1 that cross-links the alpha-helix to the wall of the beta-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 alpha-helix is located inside the pore of VDAC in the open state and remains associated with beta-strand 11 of the pore wall during voltage gating.

Place, publisher, year, edition, pages
2012. Vol. 287, no 14, 11437-11445 p.
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:uu:diva-174580DOI: 10.1074/jbc.M111.314229ISI: 000302780100072OAI: oai:DiVA.org:uu-174580DiVA: diva2:529250
Available from: 2012-05-29 Created: 2012-05-22 Last updated: 2012-05-29Bibliographically approved

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Kullman, Lisen
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