NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase
NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase
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DOI：
10.1073/pnas.2031918100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Van Doren, SR
中科院分区：
文献类型：
--
作者：
Lee, GI;Ding, ZF;Van Doren, SR
叉尖相关（FHA）结构域是在多种信号蛋白中发现的磷蛋白结合模块，其结合在苏氨酸或丝氨酸上磷酸化的伴侣。拟南芥中的激酶相关蛋白磷酸酶利用其FHA结构域对受体样激酶信号通路进行负调控，这在植物发育中是重要的。利用残余偶极耦合，以高精度和准确度确定了激酶相关蛋白磷酸酶的激酶相互作用FHA结构域（KI-FHA）自由态的溶液结构。KI-FHA是一种五链混合β折叠与六链反向平行β折叠的夹心结构。尽管仅在识别环中具有同源性，但该折叠与来自酵母和人类的检查点蛋白的FHA结构域以及Smad肿瘤抑制剂的非同源MH 2结构域共享。在整个FHA结构域和Smad MH 2结构域中共有的疏水性模式可以稳定β-夹心的核心。FHA结构域的进化痕迹分析表明，识别环中的类特异性残基可以调节其磷蛋白结合特异性。该表面与KI-FHA与磷酸苏氨酸肽配体接触的表面一致。进化痕迹分析还预测了一个意想不到的一类特异性残基的另一面FHA域。蛋白质与这些表面的相互作用可能会影响计划中跨膜信号复合物的组装以及其他含有FHA结构域的组装。
Fork nead-associated (FHA) domains are phosphoprotein-binding modules found in diverse signaling proteins that bind partners phosphorylated on threonine or serine. Kinase-associated protein phosphatase from Arabidopsis employs its FHA domain for negative regulation of receptor-like kinase signaling pathways, which are important in plant development. The solution structure of the free state of kinase-interacting FHA domain (KI-FHA) of kinase-associated protein phosphatase has been determined with high precision and accuracy using residual dipolar couplings. KI-FHA is a sandwich of a five-stranded mixed beta-sheet with a six-stranded antiparallel beta-sheet. Despite homology only in the recognition loop;, this fold is shared with FHA domains from checkpoint proteins from yeast and humans, as well as with nonhomologous MH2 domains of Smad tumor suppressors. A shared pattern of hydrophobicity throughout FHA domains and Smad MH2 domains may stabilize the core of the p-sandwich. Evolutionary trace analysis of FHA domains suggests class-specific residues in the recognition loops that could tune their phosphoprotein-binding specificity. This surface agrees with that of KI-FHA in contact with a phosphothreonine peptide ligand. Evolutionary trace analysis also predicts an unexpected swath of class-specific residues on another face of FHA domains. Protein interactions with these faces may affect assembly of transmembrane signaling complexes in plans, and in other FHA domain-containing assemblies.