The protein that forms the voltage-gated channel VDAC (or mitochondrial porin) has been purified from Neurospora crassa. At room temperature and pH 7, the circular dichroism (CD) spectrum of VDAC suspended in octyl β- glucoside is similar to those of bacterial porins, consistent with a high β- sheet content. When VDAC is reconstituted into phospholipid liposomes at pH 7, a similar CD spectrum is obtained and the liposomes are rendered permeable to sucrose. Heating VDAC in octyl β-glucoside or in liposomes results in thermal denaturation. The CD spectrum irreversibly changes to one consistent with total loss of β-sheet content, and VDAC-containing liposomes irreversibly lose sucrose permeability. When VDAC is suspended at room temperature in octyl β-glucoside at pR <5 or in sodium dodecyl sulfate at pH 7, its CD spectrum is consistent with partial loss of β-sheet content. The sucrose permeability of VDAC-containing liposomes is decreased at low pH and restored at pH 7. Similarly, the pH-dependent changes in the CD spectrum of VDAC suspended in octyl β-glucoside also are reversible. These results suggest that VDAC undergoes a reversible conformational change at low pH involving reduced β-sheet content and loss of pore-forming activity.
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