The PepSY domain: a regulator of peptidase activity in the microbial environment?

The M4 family proteins are common eubacterial metallopeptidases that are involved in a range of functions from nutrient production to pathogenicity. Typically, they consist of a propeptide with inhibitory and chaperone functions and a peptidase unit. The propeptide is cleaved but remains attached until the peptidase is secreted and can be safely activated. Here, we describe a domain in the propeptide that is likely to contain the inhibitory activity, but not the chaperone activity. It is also in many non-peptidase proteins, including Bacillus subtilis YpeB protein – a regulator of SleB spore cortex lytic enzyme – and a large number of eubacterial and archaeal cell-wall-associated and secreted proteins. We propose that it acts as a regulator of peptidase activity in the local environment and also protects the cell from lysis.