2BEC

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

2BEC の概要

• エントリーDOI: 10.2210/pdb2bec/pdb
• 分子名称: Calcineurin B homologous protein 2, Sodium/hydrogen exchanger 1, YTTRIUM (III) ION (3 entities in total)
• 機能のキーワード: calcineurin-homologous protein, calcium-binding protein, nhe1 regulating protein, metal binding protein-transport protein complex, metal binding protein/transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: P19634
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28509.78

構造登録者

Ben Ammar, Y.,Takeda, S.,Hisamitsu, T.,Mori, H.,Wakabayashi, S. (登録日: 2005-10-24, 公開日: 2006-06-27, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)