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首页> 外文期刊>Journal of Molecular Biology >The extended conformation of the 2.9-A crystal structure of the three-PASTA domain of a Ser/Thr kinase from the human pathogen Staphylococcus aureus.
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The extended conformation of the 2.9-A crystal structure of the three-PASTA domain of a Ser/Thr kinase from the human pathogen Staphylococcus aureus.

机译：人类病原体金黄色葡萄球菌的Ser / Thr激酶的三个PASTA结构域的2.9-A晶体结构的扩展构象。

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摘要

PASTA (penicillin-binding protein and serine/threonine kinase associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We report here the first crystal structure of a multiple-PASTA domain from Ser/Thr kinase, that of the protein serine/threonine kinase 1 (Stk1) from the Firmicute Staphylococcus aureus. The extended conformation of the three PASTA subunits differs strongly from the compact conformation observed in the two-PASTA domain of penicillin-binding protein PBP2x, whereas linear conformations were also reported for two-subunit fragments of the four-PASTA domain of the Actinobacteria Mycobacterium tuberculosis studied by liquid NMR. Thus, a stretched organization appears to be the signature of modular PASTA domains in Ser/Thr kinases. Signal transduction to the kinase domain is supposed to occur via dimerization and ligand binding. A conserved X-shaped crystallographic dimer stabilized by intermolecular interactions between the second PASTA subunits of each monomer is observed in the two crystal forms of Stk1 that we managed to crystallize. Extracellular PASTA domains are composed of at least two subunits, and this molecular assembly is a plausible candidate for the biological dimer. We have also performed docking experiments, which predict that the hinge regions of the PASTA domain can accommodate peptidoglycan. Finally, a three-dimensional homology molecular model of full-length Stk1 was generated, suggesting an interaction between the kinase domain and the cytoplasmic face of the plasma membrane via a eukaryotic-like juxtamembrane domain. A comprehensive activation mechanism for bacterial Ser/Thr kinases is proposed with the support of these structural data.
机译：在青霉素结合蛋白和细菌丝氨酸/苏氨酸激酶中发现的PASTA（与青霉素结合蛋白和丝氨酸/苏氨酸激酶相关）模块主要来自革兰氏阳性菌和放线菌。它们可以通过结合肽聚糖片段充当细胞外传感器。我们在这里报告来自Ser / Thr激酶的多PASTA域的第一个晶体结构，来自金黄色葡萄球菌的蛋白丝氨酸/苏氨酸激酶1（Stk1）的第一个晶体结构。三个PASTA亚基的扩展构象与在青霉素结合蛋白PBP2x的两个PASTA域中观察到的紧密构象有很大不同，而据报道放线杆菌结核分枝杆菌的四个PASTA域的两个亚基片段也存在线性构象。通过液相NMR进行了研究。因此，伸展的组织似乎是Ser / Thr激酶中模块化PASTA结构域的标志。信号转导到激酶结构域应该通过二聚化和配体结合发生。在我们设法结晶的两种Stk1晶体形式中，观察到了通过每个单体的第二个PASTA亚基之间的分子间相互作用而稳定的保守X形晶体二聚体。细胞外PASTA结构域由至少两个亚基组成，并且该分子组装是生物学二聚体的合理候选者。我们还进行了对接实验，该实验预测PASTA域的铰链区可以容纳肽聚糖。最后，生成了全长Stk1的三维同源分子模型，表明激酶域和质膜胞质表面之间通过真核样近膜域相互作用。在这些结构数据的支持下，提出了一种细菌Ser / Thr激酶的全面激活机制。

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