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

被引：27

作者：

Aleshin, Alexander E. ^{[1
]}

Gramatikova, Svetlana ^{[1
]}

Hura, Gregory L. ^{[2
]}

Bobkov, Andrey ^{[1
]}

Strongin, Alex Y. ^{[1
]}

Stec, Boguslaw ^{[1
]}

Tainer, John A. ^{[3
]}

Liddington, Robert C. ^{[1
]}

Smith, Jeffrey W. ^{[1
]}

机构：

[1] Burnham Inst Med Res, La Jolla, CA 92037 USA

[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA

来源：

STRUCTURE | 2009年 / 17卷 / 11期

关键词：

INSULIN-DEGRADING ENZYME; MITOCHONDRIAL PROCESSING PEPTIDASE; CYTOCHROME BC(1) COMPLEX; SUBSTRATE RECOGNITION; SIGNAL SEQUENCES; SCATTERING SAXS; IN-VIVO; PROTEINS; CLEAVAGE; SUBUNIT;

D O I：

10.1016/j.str.2009.09.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1465 / 1475

页数：11

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