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M604092200v1
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Papers In Press, published online ahead of print October 18, 2006
J. Biol. Chem, 10.1074/jbc.M604092200
Submitted on April 28, 2006
Accepted on October 18, 2006

Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1

Masaki Mishima, Shigeo Wakabayashi, and Chojiro Kojima

Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192

Corresponding Author: kojima{at}bs.naist.jp

Na+/H+ exchanger 1 (NHE1) regulates intracellular pH, Na+ content and cell volume. Calcineurin B homologous protein 1 (CHP1) serves as an essential cofactor which 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 report also provides the novel insight into the target binding mechanism of EF-hand proteins.


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H. C. Zaun, A. Shrier, and J. Orlowski
Calcineurin B Homologous Protein 3 Promotes the Biosynthetic Maturation, Cell Surface Stability, and Optimal Transport of the Na+/H+ Exchanger NHE1 Isoform
J. Biol. Chem., May 2, 2008; 283(18): 12456 - 12467.
[Abstract] [Full Text] [PDF]


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