Affixing N-terminal α-Helix to the Wall of the Voltage-dependent Anion Channel Does Not Prevent Its Voltage Gating*
| Autor: | Carl-Olof Hillerdal, Jeff Abramson, Tatiana K. Rostovtseva, L. Kullman, Rachna Ujwal, Oscar Teijido |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Voltage-dependent anion channel Lipid Bilayers Analytical chemistry Gating Bioenergetics Protein Engineering Biochemistry Protein Structure Secondary Voltage-Dependent Anion Channel 1 Mice Protein structure Animals Cloning Molecular Lipid bilayer Molecular Biology biology Chemistry Cell Biology Structural biology Helix Mutation Biophysics biology.protein VDAC1 Ion Channel Gating Porosity |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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