Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems.

Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems.
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DOI:
10.1016/j.str.2010.04.018
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发表时间:
2010-08-11
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Hunt JF
Hunt JF
中科院分区:
其他
文献类型:
--
作者:
Arbing MA;Handelman SK;Kuzin AP;Verdon G;Wang C;Su M;Rothenbacher FP;Abashidze M;Liu M;Hurley JM;Xiao R;Acton T;Inouye M;Montelione GT;Woychik NA;Hunt JF

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细菌毒素-抗毒素(TA)系统具有多种生理功能,包括调节细胞生长和维持外源遗传因子。序列分析表明,TA家庭是由复杂的进化关系,反映不同的TA家庭之间的功能域可能交换。我们对来自噬菌体P1的Phd-Doc、来自大肠杆菌CFT 073的HigA抗毒素和来自大肠杆菌的YeeUWV系统的YeeU进行了晶体结构分析。coli K12和福氏志贺菌证实了这一推论,并揭示了额外的,意想不到的结构关系。生长调节Doc毒素表现出与分泌的毒力因子的结构相似性,所述毒力因子对真核靶细胞有毒。Phd抗毒素具有与抑制结构上不相关的毒素的YefM和NE 2111抗毒素相同的倍数。YeeU具有抑制毒素表达的抗毒素样活性,在结构上与核糖体相互作用毒素YoeB和RelE相似。这些观察结果表明,在细菌进化过程中,TA系统之间发生了广泛的功能交换。
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 RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.
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