9.B.149 The M50 Peptidase (M50-P) Family

The M50 Peptidase (S2P-M50) family includes proteins frequently of 700-800 aas in length with six N-terminal or centrally located TMSs. However, other members of the family are relatively small (300-400 aas).  They are integral membrane zinc metaloprotease that cleave transmembrane domains in proteins. They are frequently encoded in gene clusters with lantibiotic biosynthetic enzymes and ABC transporters. For example, Streptomyces griseus encodes in the following order: an ABC-2 type transporter, an ABC-type ATPase (see TC#3.A.1.105.11), a S2P-M50 peptidase with a CBS domain (see 9.B.149.1.1), a lantibiotic synthesis protein and a lantibiotic dehydratase. Other M50 peptidases include Membrane Fusion Protein (MFP; TC# 8.A.1) domains or may have an MFP encoded in the same operon. Still others include ABC-type ATPase domains fused to them, indicating a close relationship with the transporter. Peptidase processing of bacteriocins is known in some cases to occur during transport, and the peptidase and transporter presumably form a complex in the membrane. Many bacteriocin-producing Gram-positive bacteria have ABC exporters that function with an essential MFP (Harley et al. 2000).