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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular basis of MAPK-activated protein kinase 2:p38 assembly
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Molecular basis of MAPK-activated protein kinase 2:p38 assembly

机译：MAPK激活的蛋白激酶2：p38组装的分子基础

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摘要

p3S MAPK and MAPK-activated protein kinase 2 (MK2) are key components of signaling pathways leading to many cellular responses, notably the proinf lammatory cytokine production. The physical association of p38α isoform and MK2 is believed to be physiologically important for this signaling. We report the 2.7-A resolution crystal structure of the unphosphorylated complex between p38α and MK2. These protein kinases bind "head-to-head," present their respective active sites on approximately the same side of the het-erodimer, and form extensive intermolecular interactions. Among these interactions, the MK2 lle-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38α-docking region. This binding supports the involvement of noncatalytic regions to the tight binding of the MK2:p38α binary assembly. The MK2 residues 345-365, containing the nuclear export signal, block access to the p38α active site. Some regulatory phosphorylation regions of both protein kinases engage in multiple interactions with one another in this complex. This structure gives new insights into the regulation of the protein kinases p38α and MK2, aids in the better understanding of their known cellular and biochemical studies, and provides a basis for understanding other regulatory protein-protein interactions involving signal transduction proteins.
机译：p3S MAPK和MAPK激活的蛋白激酶2（MK2）是导致许多细胞反应（尤其是促炎性前乳细胞因子产生）的信号传导途径的关键组成部分。认为p38α同工型和MK2的物理缔合对于该信号传导在生理上是重要的。我们报告了p38α和MK2之间的非磷酸化复合物的2.7-A分辨率晶体结构。这些蛋白激酶“头对头”结合，在异二聚体的大约同一侧上呈现各自的活性位点，并形成广泛的分子间相互作用。在这些相互作用中，MK2 lle-366-Ala-390（包括两部分核定位信号）与p38α对接区结合。这种结合支持非催化区域参与MK2：p38α二元组装体的紧密结合。含有核输出信号的MK2残基345-365阻止进入p38α活性位点。两种蛋白激酶的一些调节性磷酸化区域在该复合物中彼此进行多种相互作用。这种结构提供了对蛋白激酶p38α和MK2调控的新见解，有助于更好地了解其已知的细胞和生化研究，并为理解其他涉及信号转导蛋白的调控蛋白-蛋白相互作用提供了基础。

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