ArticleThe EMBO journal2006
Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- Recent advances in immunopathogenesis and clinical practice: mastering the challenge-managing of non-tuberculous mycobacteria.Frontiers in immunology · 2025Review
- Inverse regulation of SOS1 and HKT1 protein localization and stability by SOS3/CBL4 inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Host Susceptibility to Nontuberculous Mycobacterial Pulmonary Disease.Clinics in chest medicine · 2023Review
- A Novel Peptide Prevents Enterotoxin- and Inflammation-Induced Intestinal Fluid Secretion by Stimulating Sodium-Hydrogen Exchanger 3 Activity.Gastroenterology · 2023Article
- Conformational regulation and target-myristoyl switch of calcineurin B homologous protein 3.eLife · 2023Article
- Exonic splicing code and protein binding sites for calcium.Nucleic acids research · 2022Article
- How Does Our Knowledge on the NaFrontiers in physiology · 2022Review
- The intracellular lipid-binding domain of human NaCommunications biology · 2020Article
- Involvement of CHP2 in the Development of Non-Small Cell Lung Cancer and Patients' Poor Prognosis.Applied immunohistochemistry & molecular morphology : AIMM · 2020Article
- The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.PLoS pathogens · 2020Article
- Calcineurin B homologous protein 3 binds with high affinity to the CHP binding domain of the human sodium/proton exchanger NHE1.Scientific reports · 2018Article
- Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.Cold Spring Harbor perspectives in biology · 2018Review
- Phosphorylation of NHE3-SMolecular biology of the cell · 2017Article
- Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation.Journal of cell science · 2016Review
- Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity.American journal of physiology. Cell physiology · 2015Article
- The biophysical and molecular basis of intracellular pH sensing by Na+/H+ exchanger-3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na(+)/H(+) exchanger isoform 1).The Biochemical journal · 2012Article
- Na(+)/H(+) exchanger 1 directly binds to calcineurin A and activates downstream NFAT signaling, leading to cardiomyocyte hypertrophy.Molecular and cellular biology · 2012Article
- Calcineurin homologous protein: a multifunctional Ca2+-binding protein family.American journal of physiology. Renal physiology · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.