Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

被引：57

作者：

Arbing, Mark A. ^{[1
]}

Handelman, Samuel K. ^{[1
]}

Kuzin, Alexandre P. ^{[1
]}

Verdon, Gregory ^{[1
]}

Wang, Chi ^{[1
]}

Su, Min ^{[1
]}

Rothenbacher, Francesca P. ^{[3
]}

Abashidze, Mariam ^{[1
]}

Liu, Mohan ^{[3
]}

Hurley, Jennifer M. ^{[3
]}

Xiao, Rong ^{[4
,5
]}

Acton, Thomas ^{[4
,5
]}

Inouye, Masayori ^{[2
,4
,5
]}

Montelione, Gaetano T. ^{[4
,5
]}

Woychik, Nancy A. ^{[3
]}

Hunt, John F. ^{[1
]}

机构：

[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[2] Univ Med & Dent New Jersey, Dept Biochem, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA

[3] Univ Med & Dent New Jersey, Dept Mol Genet Microbiol & Immunol, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA

[4] Rutgers State Univ, Ctr Adv Technol & Med, Piscataway, NJ 08854 USA

[5] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA

来源：

STRUCTURE | 2010年 / 18卷 / 08期

基金：

美国国家卫生研究院;

关键词：

MESSENGER-RNA INTERFERASE; ESCHERICHIA-COLI; CATALYTIC SITE; PROTEIN; DNA; P1; BINDING; ASSOCIATION; AMPYLATION; MECHANISM;

D O I：

10.1016/j.str.2010.04.018

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：

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phd antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and ReIE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.

引用

页码：996 / 1010

页数：15

共 62 条

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