ArticleThe Journal of biological chemistry2011
Structure of human Na+/H+ exchanger NHE1 regulatory region in complex with calmodulin and Ca2+.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- A novel SLC9A1 mutation causes cerebellar ataxia.Journal of human genetics · 2018Trial
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- NHE1 in macrophages promotes octanal/Olfr2-induced atherosclerosis via calcium-dependent ROS and NLRP3 inflammasome activation.Scientific reports · 2025Article
- Pathophysiology of Prediabetes Hyperinsulinemia and Insulin Resistance in the Cardiovascular System.Biomedicines · 2025Review
- Cardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia.Cardiovascular diabetology · 2025Article
- Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.Cancer gene therapy · 2024Review
- ATP-mediated increase in HJournal of neurophysiology · 2024Article
- Binding by calmodulin is coupled to transient unfolding of the third FF domain of Prp40A.Protein science : a publication of the Protein Society · 2023Article
- PYK2 senses calcium through a disordered dimerization and calmodulin-binding element.Communications biology · 2022Article
- Structural basis of autoinhibition of the human NHE3-CHP1 complex.Science advances · 2022Article
- Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional regulation.Life sciences · 2022Article
- Dynamic NaeLife · 2021Article
- Calmodulin complexes with brain and muscle creatine kinase peptides.Current research in structural biology · 2021Article
- Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact.Cancers · 2020Article
- Horizontal Cell Feedback to Cone Photoreceptors in Mammalian Retina: Novel Insights From the GABA-pH Hybrid Model.Frontiers in cellular neuroscience · 2020Review
- Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019Review
- Physiological, Structural, and Functional Analysis of the Paralogous Cation-Proton Antiporters of NhaP Type fromInternational journal of molecular sciences · 2019Review
- Novel hybrid action of GABA mediates inhibitory feedback in the mammalian retina.PLoS biology · 2019Article
- Article
- Calcineurin B homologous protein 3 binds with high affinity to the CHP binding domain of the human sodium/proton exchanger NHE1.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitous mammalian Na(+)/H(+) exchanger NHE1 has critical functions in regulating intracellular pH, salt concentration, and cellular volume. The regulatory C-terminal domain of NHE1 is linked to the ion-translocating N-terminal membrane domain and acts as a scaffold for signaling complexes. A major interaction partner is calmodulin (CaM), which binds to two neighboring regions of NHE1 in a strongly Ca(2+)-dependent manner. Upon CaM binding, NHE1 is activated by a shift in sensitivity toward alkaline intracellular pH. Here we report the 2.23 Å crystal structure of the NHE1 CaM binding region (NHE1(CaMBR)) in complex with CaM and Ca(2+). The C- and N-lobes of CaM bind the first and second helix of NHE1(CaMBR), respectively. Both the NHE1 helices and the Ca(2+)-bound CaM are elongated, as confirmed by small angle x-ray scattering analysis. Our x-ray structure sheds new light on the molecular mechanisms of the phosphorylation-dependent regulation of NHE1 and enables us to propose a model of how Ca(2+) regulates NHE1 activity.
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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.