A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex.
A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex.
复制标题
DOI：
10.1021/bi902133s
复制
发表时间：
2010-03-16
期刊：
影响因子：
2.9
通讯作者：
Crosson, Sean
中科院分区：
文献类型：
--
作者：
Dalton, Kevin M.;Crosson, Sean
毒素-抗毒素（TA）系统形成了一类普遍存在的原核蛋白，在质粒遗传、环境应激反应和细胞发育中具有功能性作用。ParDE家族TA系统在质粒和细菌染色体上广泛保守，并且已经被充分表征为促进稳定质粒遗传的遗传元件。我们提出了一个晶体结构的染色体编码的ParD-ParE复杂的新月柄杆菌在2.6毫米分辨率。该TA体系在晶体和溶液中形成α2β2异源四聚体。毒素-抗毒素结合界面揭示了ParD抗毒素螺旋与帕雷毒素上的保守识别和结合沟的广泛极性和疏水接触。这种复杂的结构与相关的毒素结构的跨物种比较，确定了一个抗毒素识别和结合的亚结构域，这是保守的RelE/帕雷毒素超家族的远亲成员之间，尽管低的整体一级序列的同一性。我们进一步证明，ParD抗毒素是二聚体，稳定折叠，并在很大程度上是螺旋时，不绑定到帕雷毒素。因此，抗毒素在毒素结合后经历无序到有序转变的范例模型不适用于该染色体ParD-ParE TA系统。
Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE-family TA systems are broadly conserved on plasmids and bacterial chromosomes, and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally-encoded ParD-ParE complex from Caulobacter crescentus at 2.6 Å resolution. This TA system forms an α2β2 heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and binding groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding sub-domain that is conserved between distantly-related members of the RelE/ParE toxin superfamily despite low overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.
登录
查看更多内容
DOI：
10.1107/s0907444902016645
发表时间：
2002-11-01
影响因子：
2.2
作者：
Dauter, Z
通讯作者：
Dauter, Z
细菌程序性细胞死亡和细菌多细胞行为。
影响因子：
4.5
作者：
通讯作者：
--
影响因子：
5.6
作者：
Gronlund, H;Gerdes, K
通讯作者：
Gerdes, K
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
Li, Guang-Yao;Zhang, Yonglong;Ikura, Mitsuhiko
通讯作者：
Ikura, Mitsuhiko