HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 4, 2741-2751, January 26, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/4/2741    most recent M604092200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mishima, M. Articles by Kojima, C. Search for Related Content PubMed PubMed Citation Articles by Mishima, M. Articles by Kojima, C. Social Bookmarking                      What's this?

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 Kojima¹

From the Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan and Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan

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.

Received for publication, April 28, 2006 , and in revised form, October 6, 2006.

The atomic coordinates and structure factors (code 2E30) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported in part by grants-in-aid for Scientific Research on Priority Area and the 21st Century of Excellence (COE) Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (to M. M. and C. K.), and Grant nano-001 for Research on Advanced Medical Technology from the Ministry of Health, Labor and Welfare of Japan and Grant-in-aid for Priority Areas 13142210 for Scientific Research from the MEXT (to S. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Figs. S2 and S3.

¹ To whom correspondence should be addressed: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan. Tel.: 81-743-72-5571; Fax: 81-743-72-5579; E-mail: kojima{at}bs.naist.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]