Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel%26apos;s Gating Behavior

作者：Mertins Barbara; Psakis Georgios; Grosse Wolfgang; Back Katrin Christiane; Salisowski Anastasia; Reiss Philipp; Koert Ulrich; Essen Lars Oliver^*

来源：PLos One, 2012, 7(10): e47938.

DOI：10.1371/journal.pone.0047938

Since the solution of the molecular structures of members of the voltage dependent anion channels (VDACs), the N-terminal alpha-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%26apos;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 %26quot;asymmetric%26quot; gating behavior, with closure only at one electric fields orientation depending on the channel%26apos;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%26apos;s gating behavior.

• 出版日期2012-10-23