2BEC

Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation

Summary for 2BEC

• Entry DOI: 10.2210/pdb2bec/pdb
• Descriptor: Calcineurin B homologous protein 2, Sodium/hydrogen exchanger 1, YTTRIUM (III) ION (3 entities in total)
• Functional Keywords: calcineurin-homologous protein, calcium-binding protein, nhe1 regulating protein, metal binding protein-transport protein complex, metal binding protein/transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Multi-pass membrane protein: P19634
• Total number of polymer chains: 2
• Total formula weight: 28509.78

Authors

Ben Ammar, Y.,Takeda, S.,Hisamitsu, T.,Mori, H.,Wakabayashi, S. (deposition date: 2005-10-24, release date: 2006-06-27, Last modification date: 2024-03-13)

Primary citation

Ben Ammar, Y.,Takeda, S.,Hisamitsu, T.,Mori, H.,Wakabayashi, S.
Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation
Embo J., 25:2315-2325, 2006

PubMed Abstract: The plasma membrane Na+/H+ exchangers (NHE) require calcineurin B homologous protein (CHP) as an obligatory binding partner for ion transport. Here, we report the first crystal structure of CHP (CHP2 isoform) in complex with its binding domain in NHE1. We show that the cytoplasmic alpha-helix of NHE1 is inserted into the hydrophobic cleft formed by N- and C-lobes of CHP2 and that the size and shape of this crevice together with hydrogen bond formation at multiple positions assure a high degree of specificity for interaction with NHE members. Structure-based mutagenesis revealed the importance of hydrophobic interactions between CHP/NHE1 for the function of NHE1. Furthermore, the crystal structure shows the existence of a protruding CHP-unique region, and deletion of this region in CHP2 inhibited the NHE1 activity by inducing the acidic shift of intracellular pH dependence, while preserving interaction with NHE1. These findings suggest that CHP serves as an obligatory subunit that is required both for supporting the basic activity and regulating the pH-sensing of NHE1 via interactions between distinct parts of these proteins.

PubMed: 16710297
DOI: 10.1038/sj.emboj.7601145

Experimental method

X-RAY DIFFRACTION (2.7 Å)