Fido, a novel AMPylation domain common to fic, doc, and AvrB.
Fido, a novel AMPylation domain common to fic, doc, and AvrB.
复制标题
DOI：
10.1371/journal.pone.0005818
复制
发表时间：
2009-06-05
期刊：
影响因子：
3.7
通讯作者：
Grishin NV
中科院分区：
文献类型：
--
作者：
Kinch LN;Yarbrough ML;Orth K;Grishin NV
副溶血性弧菌III型分泌效应子VopS含有一个FIC结构域，它与AMP共价修饰Rho GTP酶苏氨酸，从而抑制宿主细胞中的下游信号事件。VopS结构域包括一个保守的序列基序(HPFX[D/E]GN[G/K]R)，有助于AMP化。FIC结构域存在于多种物种中，包括细菌、一些古生物和后生动物。我们发现AMP化活性延伸到果蝇CG9523中的真核FIC结构域，并使用基于序列和结构的计算方法来识别DOC毒素和III型效应器AvrB中的相关结构域。有助于AMP化的保守序列基序将FIC与DOC结合起来。虽然AvrB缺乏这个基序，但它的结构显示了与FIC和DOC折叠相似的拓扑结构。AvrB与其宿主毒力靶标的多肽片段结合的方式与Fc结合多肽底物的方式相似。AvrB还从多肽结合部位附近的结合的ADP配体上定向磷酸基团，并定位在与结合的FIC磷酸类似的位置。证实了真核细胞结构域的AMP化活性，这表明VopS效应器已经利用了一种新的宿主翻译后修饰。FIC结构域相关结构使我们能够深入了解AMPyl化活性部位以及VopSfic结构域与其宿主GTPase靶标的相互作用。这些结果表明，Fc、DOC和AvrB起源于共同的祖先，该祖先已经进化为AMPylate蛋白底物。
The Vibrio parahaemolyticus type III secreted effector VopS contains a fic domain that covalently modifies Rho GTPase threonine with AMP to inhibit downstream signaling events in host cells. The VopS fic domain includes a conserved sequence motif (HPFx[D/E]GN[G/K]R) that contributes to AMPylation. Fic domains are found in a variety of species, including bacteria, a few archaea, and metazoan eukaryotes. We show that the AMPylation activity extends to a eukaryotic fic domain in Drosophila melanogaster CG9523, and use sequence and structure based computational methods to identify related domains in doc toxins and the type III effector AvrB. The conserved sequence motif that contributes to AMPylation unites fic with doc. Although AvrB lacks this motif, its structure reveals a similar topology to the fic and doc folds. AvrB binds to a peptide fragment of its host virulence target in a similar manner as fic binds peptide substrate. AvrB also orients a phosphate group from a bound ADP ligand near the peptide-binding site and in a similar position as a bound fic phosphate. The demonstrated eukaryotic fic domain AMPylation activity suggests that the VopS effector has exploited a novel host posttranslational modification. Fic domain-related structures give insight to the AMPylation active site and to the VopS fic domain interaction with its host GTPase target. These results suggest that fic, doc, and AvrB stem from a common ancestor that has evolved to AMPylate protein substrates.
登录
查看更多内容
影响因子：
3
作者：
Kajan, Laszlo;Rychlewski, Leszek
通讯作者：
Rychlewski, Leszek
影响因子：
5.7
作者：
Lee, CC;Wood, MD;Katagiri, F
通讯作者：
Katagiri, F
影响因子：
14.9
作者：
Ginalski, K;von Grotthuss, M;Rychlewski, L
通讯作者：
Rychlewski, L
影响因子：
12.3
作者：
Anantharaman V;Aravind L
通讯作者：
Aravind L
影响因子：
5.6
作者：
LEHNHERR, H;MAGUIN, E;YARMOLINSKY, MB
通讯作者：
YARMOLINSKY, MB