FIGURE 6.

Models of furin activation. Three potential models of furin activation are considered. The dissociation model (top panel) posits that PRO^FUR dissociates from MAT^FUR after the pH sensor is protonated and then reassociates in a different orientation so that the propeptide can be cleaved. The cis and trans models of processing (center and bottom panels, respectively), in contrast, both suggest that protonation of the pH sensor drives an unfolding event that allows the cleavage site loop to become accessible to the active site, either for its own MAT^FUR to be cleaved in cis (center panel), or to a second molecule of MAT^FUR to be cleaved in trans. Only after the propeptide is cleaved does it dissociate from the protease.