Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel's Gating Behavior

Barbara Mertins, Georgios Psakis, Wolfgang Grosse, Katrin Christiane Back, Anastasia Salisowski, Philipp Reiss, Ulrich Koert, Lars Oliver Essen

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 field́s 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.

LanguageEnglish
Article numbere47938
Number of pages14
JournalPLoS One
Volume7
Issue number10
DOIs
Publication statusPublished - 23 Oct 2012
Externally publishedYes

Fingerprint

crosslinking
Cysteine
cysteine
Voltage-Dependent Anion Channels
lipid bilayers
Lipid bilayers
Lipid Bilayers
Molecular Structure
chemical structure
anions
Molecular structure
engineering
alpha-Helical Protein Conformation

Cite this

Mertins, B., Psakis, G., Grosse, W., Back, K. C., Salisowski, A., Reiss, P., ... Essen, L. O. (2012). Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel's Gating Behavior. PLoS One, 7(10), [e47938]. https://doi.org/10.1371/journal.pone.0047938
Mertins, Barbara ; Psakis, Georgios ; Grosse, Wolfgang ; Back, Katrin Christiane ; Salisowski, Anastasia ; Reiss, Philipp ; Koert, Ulrich ; Essen, Lars Oliver. / Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel's Gating Behavior. In: PLoS One. 2012 ; Vol. 7, No. 10.
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Mertins, B, Psakis, G, Grosse, W, Back, KC, Salisowski, A, Reiss, P, Koert, U & Essen, LO 2012, 'Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel's Gating Behavior', PLoS One, vol. 7, no. 10, e47938. https://doi.org/10.1371/journal.pone.0047938

Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel's Gating Behavior. / Mertins, Barbara; Psakis, Georgios; Grosse, Wolfgang; Back, Katrin Christiane; Salisowski, Anastasia; Reiss, Philipp; Koert, Ulrich; Essen, Lars Oliver.

In: PLoS One, Vol. 7, No. 10, e47938, 23.10.2012.

Research output: Contribution to journalArticle

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AU - Reiss, Philipp

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