Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3
Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3
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DOI：
10.1073/pnas.0510506103
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发表时间：
2006-04-04
影响因子：
11.1
通讯作者：
Zhang, ZY
中科院分区：
文献类型：
--
作者：
Liu, SJ;Sun, JP;Zhang, ZY
有丝分裂原活化蛋白（MAP）激酶是细胞增殖、应激反应和分化的信号转导途径的中心组分。信号传导效率和特异性在很大程度上通过单个MAP激酶与其同源激酶、磷酸酶、支架蛋白和底物中的激酶相互作用基序（KIM）（R/K）（2-3）-X1-6-Phi（A）-X-Phi（B）之间的对接相互作用来调节。我们已经确定了晶体结构的细胞外信号调节蛋白激酶2结合到KIM肽从MAP激酶磷酸酶3，细胞外信号调节蛋白激酶2特异性磷酸酶。该结构显示，KIM对接位点位于激酶催化口袋对面的非催化区域，由一个高度酸性的补丁和一个疏水沟组成，分别与KIM序列中的碱性和Phi（A）-X-Phi（B）残基接合。在结构中观察到的特定对接相互作用巩固了所有已知的生物化学数据。此外，结构比较表明，KIM对接位点在所有MAP激酶中是保守的。结果建立了一个结构模型，了解MAP激酶如何与他们的监管机构和底物相互作用，并提供了新的见解如何MAP激酶对接特异性可以实现。
Mitogen-activated protein (MAP) kinases are central components of signal transduction pathways for cell proliferation, stress responses, and differentiation. Signaling efficiency and specificity are modulated in large part by docking interactions between individual MAP kinase and the kinase interaction motif (KIM), (R/K)(2-3)-X1-6-Phi(A)-X-Phi(B), in its cognate kinases, phosphatases, scaffolding proteins, and substrates. We have determined the crystal structure of extracellular signal-regulated protein kinase 2 bound to the KIM peptide from MAP kinase phosphatase 3, an extracellular signal-regulated protein kinase 2-specific phosphatase. The structure reveals that the KIM docking site, situated in a noncatalytic region opposite of the kinase catalytic pocket, is comprised of a highly acidic patch and a hydrophobic groove, which engage the basic and Phi(A)-X-Phi(B) residues, respectively, in the KIM sequence. The specific docking interactions observed in the structure consolidate all known biochemical data. In addition, structural comparison indicates that the KIM docking site is conserved in all MAP kinases. The results establish a structural model for understanding how MAP kinases interact with their regulators and substrates and provide new insights into how MAP kinase docking specificity can be achieved.