title: Flexibility of the N-terminal mVDAC1 segment controls the channel's gating behavior.
abstract: Since the solution of the molecular structures of members of the voltage dependent anion channels (VDACs), the N-terminal α-helix has been the main focus of attention, since its strategic location, in combination with its putative conformational flexibility, could define or control the channel's gating characteristics. Through engineering of two double-cysteine mVDAC1 variants we achieved fixing of the N-terminal segment at the bottom and midpoint of the pore. Whilst cross-linking at the midpoint resulted in the channel remaining constitutively open, cross-linking at the base resulted in an "asymmetric" gating behavior, with closure only at one electric field's orientation depending on the channel's orientation in the lipid bilayer. Additionally, and while the native channel adopts several well-defined closed states (S1 and S2), the cross-linked variants showed upon closure a clear preference for the S2 state. With native-channel characteristics restored following reduction of the cysteines, it is evident that the conformational flexibility of the N-terminal segment plays indeed a major part in the control of the channel's gating behavior.
authors.affiliation: Department of Chemistry, Philipps University Marburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mertins
authors.forename: Georgios
authors.initials: G
authors.lastname: Psakis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Grosse
authors.forename: Katrin Christiane
authors.initials: KC
authors.lastname: Back
authors.forename: Anastasia
authors.initials: A
authors.lastname: Salisowski
authors.forename: Philipp
authors.initials: P
authors.lastname: Reiss
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koert
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Essen
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005818:Genetic Engineering; D002479:Inclusion Bodies / Q000378:metabolism; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C494763:Vdac1 protein, mouse; D050995:Voltage-Dependent Anion Channel 1