ArticleScience advances2022
Structural basis of autoinhibition of the human NHE3-CHP1 complex.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Cryo-EM structure of human NaNature communications · 2026Article
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.Nature communications · 2026Article
- CHP1 promotes lipid droplet growth and regulates the localization of key enzymes for triacylglycerol synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PIPNature communications · 2025Article
- Structure and mechanism of the osmoregulated choline transporter BetT.Science advances · 2024Article
- Structures of a sperm-specific sodium-hydrogen exchanger.Cell insight · 2024Article
- Structure and mechanism of the KNature communications · 2024Article
- Review
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- Article
- Structural basis for the activity regulation of Salt Overly Sensitive 1 in Arabidopsis salt tolerance.Nature plants · 2023Article
- Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) NaNature plants · 2023Article
- Article
- Architecture and rearrangements of a sperm-specific NaResearch square · 2023Article
- NaInternational journal of molecular sciences · 2023Review
- Architecture and autoinhibitory mechanism of the plasma membrane NaNature communications · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sodium-proton exchanger 3 (NHE3/SLC9A3) located in the apical membrane of renal and gastrointestinal epithelia mediates salt and fluid absorption and regulates pH homeostasis. As an auxiliary regulatory factor of NHE proteins, calcineurin B homologous protein 1 (CHP1) facilitates NHE3 maturation, plasmalemmal expression, and pH sensitivity. Dysfunctions of NHE3 are associated with renal and digestive system disorders. Here, we report the cryo-electron microscopy structure of the human NHE3-CHP1 complex in its inward-facing conformation. We found that a cytosolic helix-loop-helix motif in NHE3 blocks the intracellular cavity formed between the core and dimerization domains, functioning as an autoinhibitory element and hindering substrate transport. Furthermore, two phosphatidylinositol molecules are found to bind to the peripheric juxtamembrane sides of the complex, function as anchors to stabilize the complex, and may thus enhance its transport activity.
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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.