Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions
Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions
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DOI：
10.1016/j.jmb.2004.07.068
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发表时间：
2004-10-01
影响因子：
5.6
通讯作者：
Hogan, PG
中科院分区：
文献类型：
--
作者：
Li, HM;Rao, AJ;Hogan, PG
钙调神经磷酸酶是一种磷蛋白磷酸酶，可将细胞内 Ca 信号引导至多种生物途径。已知钙调磷酸酶可直接与其活化 T 细胞的底物核因子（NEAT 或 NFATc）、其他底物以及包括 AKAP79 和 Cabin1/cain 在内的多种靶向和支架蛋白相互作用。钙调磷酸酶-NFAT 相互作用取决于对 NFAT 家族蛋白和某些其他钙调磷酸酶相互作用蛋白中存在的 PxIxIT 序列基序的识别。在这里，我们定义了钙调神经磷酸酶与 NFAT 以及与具有 PxIxIT 基序的其他蛋白质相互作用的结构基础。钙调神经磷酸酶-PxIxIT 接触与蛋白磷酸酶 1 与其调节蛋白的接触有直接的平行关系，表明这些相关磷酸酶的进化涉及祖先对接位点的局部重塑。 (C) 2004 Elsevier Ltd. 保留所有权利。
Calcineurin is a phosphoprotein phosphatase that channels intracellular Ca signals into multiple biological pathways. Calcineurin is known to interact directly with its substrate nuclear factor of activated T cells (NEAT or NFATc), with other substrates, and with several targeting and scaffold proteins including AKAP79 and Cabin1/cain. The calcineurin-NFAT interaction depends on recognition of a PxIxIT sequence motif present in NFAT-family proteins and in certain other calcineurin-interacting proteins. Here, we define the structural basis for the interaction of calcineurin with NFAT and with other proteins possessing the PxIxIT motif. The calcineurin-PxIxIT contact has a direct parallel in the contact of protein phosphatase 1 with its regulatory proteins, suggesting that the evolution of these related phosphatases involved local remodelling of an ancestral docking site. (C) 2004 Elsevier Ltd. All rights reserved.