ArticleThe Journal of biological chemistry2011
Structural modeling and electron paramagnetic resonance spectroscopy of the human Na+/H+ exchanger isoform 1, NHE1.
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 16 papers.
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16 citing papers in PubMed, 51 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- NDPACX: a newly defined X-linked Parkinsonian syndrome associated withBrain communications · 2025Review
- The Remaining Conundrum of the Role of the NaReviews in cardiovascular medicine · 2022Review
- Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional regulation.Life sciences · 2022Article
- Off-target effects of sodium-glucose co-transporter 2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart.Cardiovascular research · 2021Article
- Role of Genetic Mutations of the NaMolecular and cellular biochemistry · 2021Review
- Assorted dysfunctions of endosomal alkali cation/proton exchangerThe Journal of biological chemistry · 2020Article
- Acidic residues of extracellular loop 3 of the NaMolecular and cellular biochemistry · 2020Article
- Interplay between hydrophobicity and the positive-inside rule in determining membrane-protein topology.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A Christianson syndrome-linked deletion mutation (∆(287)ES(288)) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death.Molecular neurodegeneration · 2016Article
- Determinants of Cation Permeation and Drug Sensitivity in Predicted Transmembrane Helix 9 and Adjoining Exofacial Re-entrant Loop 5 of Na+/H+ Exchanger NHE1.The Journal of biological chemistry · 2015Article
- Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule.Cellular and molecular life sciences : CMLS · 2015Review
- Na(+)/H(+) exchange and hypoxic pulmonary hypertension.Pulmonary circulation · 2015Review
- Functional role and analysis of cysteine residues of the salt tolerance protein Sod2.Molecular and cellular biochemistry · 2014Article
- Antimitochondrial antibody recognition and structural integrity of the inner lipoyl domain of the E2 subunit of pyruvate dehydrogenase complex.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Two conflicting NHE1 model structures: compatibility with experimental data and implications for the transport mechanism.The Journal of biological chemistry · 2011Article
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11 authors at 3 institutions in 3 countries.
Funding
Abstract
We previously presented evidence that transmembrane domain (TM) IV and TM X-XI are important for inhibitor binding and ion transport by the human Na(+)/H(+) exchanger, hNHE1 (Pedersen, S. F., King, S. A., Nygaard, E. B., Rigor, R. R., and Cala, P. M. (2007) J. Biol. Chem. 282, 19716-19727). Here, we present a structural model of the transmembrane part of hNHE1 that further supports this conclusion. The hNHE1 model was based on the crystal structure of the Escherichia coli Na(+)/H(+) antiporter, NhaA, and previous cysteine scanning accessibility studies of hNHE1 and was validated by EPR spectroscopy of spin labels in TM IV and TM XI, as well as by functional analysis of hNHE1 mutants. Removal of all endogenous cysteines in hNHE1, introduction of the mutations A173C (TM IV) and/or I461C (TM XI), and expression of the constructs in mammalian cells resulted in functional hNHE1 proteins. The distance between these spin labels was ∼15 A, confirming that TM IV and TM XI are in close proximity. This distance was decreased both at pH 5.1 and in the presence of the NHE1 inhibitor cariporide. A similar TM IV·TM XI distance and a similar change upon a pH shift were found for the cariporide-insensitive Pleuronectes americanus (pa) NHE1; however, in paNHE1, cariporide had no effect on TM IV·TM XI distance. The central role of the TM IV·TM XI arrangement was confirmed by the partial loss of function upon mutation of Arg(425), which the model predicts stabilizes this arrangement. The data are consistent with a role for TM IV and TM XI rearrangements coincident with ion translocation and inhibitor binding by hNHE1.
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