Understanding mechanisms of pH sensing in proprotein convertases

The Proprotein Convertases are members of the subtilase superfamily of serine endoproteases, and are responsible for the processing and activation of myriad secreted proteins and peptides within the cell. The necessity for precise spatiotemporal cleavage of substrates mandates the activity of the proprotein convertases be likewise stringently controlled; like all subtilases, the propeptide plays a critical role in the compartment-specific folding, trafficking, and activation of the Proprotein Convertases. In the following dissertation, I present my contribution to our understanding of how the Proprotein Convertases have evolved regulate their activation via their propeptides.