Teijido Hermida, ÓscarUjwal, RachnaHillerdal, Carl-OlofKullman, LisenRostovtseva, Tatiana K.Abramson, Jeff2025-01-292025-01-292012-03-30Teijido, O., Ujwal, R., Hillerdal, C. O., Kullman, L., Rostovtseva, T. K., Abramson, J. (2012). Affixing N-terminal a-helix to the wall of the voltage-dependent anion channel does not prevent its voltage gating. Journal of the Biological Chemistry, 287(14), 11437-11445. https://doi.org/10.1074/jbc.M111.314229.0021-925810.1074/jbc.M111.314229https://academica-e.unavarra.es/handle/2454/53142The 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 gatingapplication/pdfapplication/zipengThis is an open access article under the CC BY license.ADPATPBioenergeticsBiophysicsStructural biologyStructural dynamicsVoltage dependencyVoltage-dependent anion channelinfo:eu-repo/semantics/article2025-01-29info:eu-repo/semantics/openAccess