Premium
Structural and functional aspects of the Na+/H+ exchanger 1 and its obligatory binding partner CHP
Author(s) -
Wakabayashi Shigeo,
Ben Ammar Youssef,
Hisamitsu Takashi,
Takeda Soichi
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a243-a
Subject(s) - gene isoform , cytosol , cytoplasm , chemistry , intracellular ph , intracellular , biochemistry , sodium–hydrogen antiporter , transporter , microbiology and biotechnology , biophysics , biology , gene , enzyme , sodium , organic chemistry
The Na+/H+ exchanger (NHE, SLC9 family) is an electroneutral transporter that catalyzes the exchange of Na+ and H+ and regulate the ionic homeostasis such as regulation of intracellular pH (pHi), Na+ concentration and cell volume. In recent years, we have focused on several essential factors indispensable for supporting the physiological activity of the ubiquitous isoform NHE1. We obtained evidence that at least three processes are necessary: interaction of multiple protons with the regulatory sites in the cytoplasmic side of NHE1, dimerization of NHE1 and interaction of calcineurin B‐homologous protein CHP with the juxtamembrane cytoplasmic region. CHP is one of EF‐hand Ca2+ binding proteins and now at least three isoforms are known. While CHP1 is ubiquitously expressed, the expression CHP2 and CHP3 (tescalcin) are restricted to particular tissues. We recently suggested that CHP2 is highly expressed in cancer cells and may be involved in maintenance of high pHi in these cells. More recently, we determined the crystal structure of CHP2 complexed with its cytosolic region (aa 503‐545) at 2.7 Å using MAD and clarified the molecular basis for producing the target specificity of related Ca2+ binding proteins at atomic level. In this mini‐symposium, we will particularly focus on the crystal structure of the CHP/NHE1‐peptide complex and insights into pH regulation of NHE1.