ON THE STRUCTURE AND GATING MECHANISM OF THE MITOCHONDRIAL CHANNEL, VDAC

There is considerable evidence that the voltage-gated mitochondrial ch annel VDAC forms a beta-barrel pore. Inferences about the number and t ilt of beta-strands can be drawn from comparisons with bacterial beta- barrel pores whose structures have been determined by x-ray crystallog raphy. A structural model for VDAC is proposed (based on sequence anal ysis and electron crystallography) in which the open state is like tha t of bacterial porins with several important differences. Because VDAC does not occur as close-packed trimers, there are probably fewer inte rpore contacts than in the bacterial porins. VDAC also appears to lack a large, fixed intraluminal segment and may not have as extensive a r egion of uniformly 35 degrees-tilted beta-strands as do the bacterial porins. These structural differences would be expected to render VDAC' s beta-barrel less stable than its bacterial counterparts, making majo r conformational changes like those associated with gating more energe tically feasible. A possible gating mechanism is suggested in which mo vement of the N-terminal alpha-helix out of the lumen wall triggers la rger-scale structural changes.