calcineurin B homologous protein 1 (CHP1), Na+/H+ exchanger (NHE), cytoplasmic region peptide complex
Human (Homo sapiens)
The regulation of cytoplasmic pH, level of sodium ion, and osmotic pressure is indispensable for normal cell behavior, and this kind of function to maintain the homeostatis of intracellular ion circumstance mainly relies on Na+/H+ exchangers (NHEs). They exchange intracellular hydrogen ion and extracellular sodium ion at equal rate using transmembrane sodium concentration gradient.
One of the major NHE in higher organisms, NHE1 (Na+/H+ exchanger 1), is a 12 transmembrane protein exists in various tissues. It is known that NHE1 may become a risk factor of various disease such as heart disease, and the defect of NEH1 gene in mice may lead kinetic ataxia and epileptic convulsion. Thus the mechanism of activity control is interested also in medical sight. Though it is not well known, the binding of C terminal intracellular region of NHE1 to the calcineurin B homologous protein 1 (CHP1) is suggested to necessary for NHE1 activation. The structure of NHE1 C terminal cytoplasmic region bound to CHP1 complex may support to elucidate the NHE1 activation mechanism.
CHP is composed of two domains, N lobe of N terminus and C lobe of C terminus. Each of them includes two EF hand motifs, known as calcium binding motif, which are connected with CHP specific long loop region called CHP loop. Though the cytoplasmic region of NHE1 is disordered its alone, the complex with CHP1 constructs amphipathic alpha helix of which hydrophobic plane is gone in the hydrophobic pocket. The structural change in the NHE1 cytoplasmic region caused by CHP1 binding suggests to play a key role in NHE1 activation.
Protein Data Bank (PDB)
author: Kokoro Hayashi, translated by Takahiro Kudou