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.
Aleshin
Alexander E
AE
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Gramatikova
Svetlana
S
Hura
Gregory L
GL
Bobkov
Andrey
A
Strongin
Alex Y
AY
Stec
Boguslaw
B
Tainer
John A
JA
Liddington
Robert C
RC
Smith
Jeffrey W
JW
D000595:Amino Acid Sequence; D001407:Bacillus / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry*; D001483:Base Sequence; D019295:Computational Biology; D003461:Crystallography; D019281:Dimerization; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D008666:Metalloendopeptidases; D015032:Zinc