Crystal and solution structures of a prokaryotic M16B peptidase: an open and shut case

Structure. 2009 Nov 11;17(11):1465-75. doi: 10.1016/j.str.2009.09.009.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacillus / enzymology*
  • Bacterial Proteins / chemistry*
  • Base Sequence
  • Computational Biology
  • Crystallography
  • Dimerization
  • Metalloendopeptidases / chemistry*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Conformation*
  • Sequence Alignment
  • Zinc / metabolism

Substances

  • Bacterial Proteins
  • Metalloendopeptidases
  • Zinc

Associated data

  • PDB/3HDI