On a fully closed state of native human type-1 VDAC enriched in Nonidet P40

There is indication that human type-1 VDAC/Porin31HL complexes, when purified from highly enriched cell membrane preparations of human B-lymphocytes by classical ion-exchange chromatography in the detergent Nonidet P40, rest in fully closed state, its N-terminus being accessible for mAbs. Cholesterol appears to be involved as a channel modulator. The channel switches to anion-selective or open state while being incorporated into black membranes at zero transmembrane potential. In this case, its N-terminus is hidden in the channel lumen. The cation-selective or closed state can be induced by transmembrane potentials beyond 30 mV, the N-terminus putatively now being positioned outside the channel lumen. The latter situation might allow one to decide if type-1 VDAC, preincubated with adequate antibodies against its N-terminal part, would enter black membranes in fully closed state or stay in the application medium. respectively, may be complexed to dimers. (C) 2012 Elsevier Inc. All rights reserved.