Crystal and Solution Structures of a Prokaryotic M16B Peptidase: an Open and Shut Case

The M16 family of zinc peptidases comprises a pair of homologous domains that form two halves of a clam-shell surrounding the active site. The M16A and M16C subfamilies form one class (peptidasomes): they degrade 30-70 residue peptides, and adopt both open and closed conformations. The eukaryotic M16B subfamily forms a second class (processing proteases): they adopt a single partly-open conformation that enables them to cleave signal sequences from larger proteins. Here, we report the solution and crystal structures of a prokaryotic M16B peptidase, and demonstrate that it has features of both classes: thus, it forms stable open homodimers; in solution that resemble the processing proteases; but the clam-shell closes upon binding substrate, a feature of the M16A/C peptidasomes. Moreover, clam-shell closure is required for proteolytic activity. We predict that other prokaryotic M16B family members will form dimeric peptidasomes, and propose a model for the evolution of the M16 family.