Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1
Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1
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DOI：
10.1074/jbc.m604092200
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发表时间：
2007-01-26
影响因子：
4.8
通讯作者：
Kojima, Chojiro
中科院分区：
文献类型：
--
作者：
Mishima, Masaki;Wakabayashi, Shigeo;Kojima, Chojiro
Na+/H+交换器1（NHE 1）调节细胞内pH、Na+含量和细胞体积。钙调神经磷酸酶B同源蛋白1（CHP 1）作为一种必需的辅因子，通过直接结合NHE 1的胞质质膜区域，在生理条件下促进NHE 1交换活性。在这里，我们描述的解决方案结构的胞质质膜区域NHE 1与CHP 1复合。NHE 1的区域形成两亲性螺旋，这是由CHP 1结合诱导的，并且CHP 1具有由EF-手螺旋形成的大的疏水裂缝。NHE 1螺旋的非极性侧参与与CHP 1裂缝的广泛疏水相互作用。我们认为，螺旋形成的NHE 1的胞质区域的CHP 1是一个先决条件，产生的活性形式的NHE 1。在这项研究中详细的分子识别也提供了新的见解EF手蛋白的靶结合机制。
Na+/H+ exchanger 1 (NHE1) regulates intracellular pH, Na+ content, and cell volume. Calcineurin B homologous protein 1 (CHP1) serves as an essential cofactor that facilitates NHE1 exchange activity under physiological conditions by direct binding to the cytoplasmic juxtamembrane region of NHE1. Here we describe the solution structure of the cytoplasmic juxtamembrane region of NHE1 complexed with CHP1. The region of NHE1 forms an amphipathic helix, which is induced by CHP1 binding, and CHP1 possesses a large hydrophobic cleft formed by EF-hand helices. The apolar side of the NHE1 helix participates in extensive hydrophobic interactions with the cleft of CHP1. We suggest that helix formation of the cytoplasmic region of NHE1 by CHP1 is a prerequisite for generating the active form of NHE1. The molecular recognition detailed in this study also provides novel insight into the target binding mechanism of EF-hand proteins.