Figure 1

Models illustrating the different cellular fates of PA and DNI. Top: Upon binding cellular receptors (step 1), PA is cleaved (step 2). The small fragments diffuse away, and the cell-bound fraction self-assembles into heptameric cores termed (PA₆₃)₇ (step 3). The heptamers then undergo receptor-mediated endocytosis (step 4). Once inside the acidic endosomal compartment, the PA heptamers change conformation and insert into the endosomal membrane (step 5). Bottom: DNI, similar to PA, enters the endosome (steps 1–4). However, DNI heptamers do not undergo the necessary conformational changes for insertion into the membrane and therefore remain trapped inside the endosome.