The BH3-only proteins initiate apoptosis through binding to pro-apoptotic Bax or Bak and recruiting them to the membrane, where they form large complexes that generate membrane spanning pores, hence making the membrane permeable [11].
To investigate the structural basis for cation-binding within the type IID ATPase subfamily, we used homology modeling to identify a highly conserved cation-binding pocket between membrane helix (MH) 4 and MH 6 of the membrane-spanning pore of PpENA1.
These toxin complexes are internalized by receptor-mediated endocytosis and LF is delivered to the cytosol after translocating through a membrane-spanning pore formed by the heptamer [5], [6].
Previously it was noted that the pH profile of anthrax toxin pore formation was consistent with the titration of histidines and that there are several histidines (H299, H304, H310, and H336), located in the 285 340 region of PA which forms the membrane-spanning pore [17], [18].
While having the same structure at the selectivity filter region, the membrane-spanning pore of GsuK has several unique structural features as compared to other K+ channels.
Trp346 is of particular interest because of its proximity to the CMG2 binding interface, and because it forms part of the membrane-spanning pore.
Protective antigen (PA) mediates entry of edema factor (EF) and lethal factor (LF) into the cytoplasmic space of the cells through the formation of a membrane-spanning pore.
(B ) Comparison of the translational distances between the gating ring and the membrane-spanning pore in GsuK (left, L97D mutant) and MthK (right).
PA is capable of undergoing several structural changes, including oligomerization to either a heptameric or octameric structure called the prepore, and at acidic pH a major conformational change to form a membrane-spanning pore.
The PA63 prepore recruits the toxin's enzymatic moieties, edema factor (EF) and lethal factor (LF), and upon reaching an intracellular compartment converts into a membrane-spanning pore that translocates the enzymes to the cell cytosol.
