ArticleThe Journal of biological chemistry2017
An amphipathic α-helix directs palmitoylation of the large intracellular loop of the sodium/calcium exchanger.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Nanobody-thioesterase chimeras to specifically target protein palmitoylation.Nature communications · 2025Article
- Palmitoylation and regulation of potassium-dependent sodium/calcium exchangers (NCKX).Bioscience reports · 2025Article
- LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.EMBO molecular medicine · 2023Article
- The role of an amphiphilic helix and transmembrane region in the efficient acylation of the M2 protein from influenza virus.Scientific reports · 2023Article
- Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.Nature communications · 2023Article
- Palmitoylation of solute carriers.Biochemical pharmacology · 2023Review
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An inducible amphipathic α-helix mediates subcellular targeting and membrane binding of RPE65.Life science alliance · 2023Article
- Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.International journal of molecular sciences · 2022Review
- Proton-modulated interactions of ions with transport sites of prokaryotic and eukaryotic NCX prototypes.Cell calcium · 2021Article
- A novel yeast-based high-throughput method for the identification of protein palmitoylation inhibitors.Open biology · 2021Article
- Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1.Cell calcium · 2021Article
- Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function.Membranes · 2021Review
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- Dynamic Palmitoylation of the Sodium-Calcium Exchanger Modulates Its Structure, Affinity for Lipid-Ordered Domains, and Inhibition by XIP.Cell reports · 2020Article
- Modulation of the cardiac NaCell calcium · 2020Review
- Article
- Palmitoylation: A Fatty Regulator of Myocardial Electrophysiology.Frontiers in physiology · 2020Review
- Spatial organization of palmitoyl acyl transferases governs substrate localization and function.Molecular membrane biology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The electrogenic sodium/calcium exchanger (NCX) mediates bidirectional calcium transport controlled by the transmembrane sodium gradient. NCX inactivation occurs in the absence of phosphatidylinositol 4,5-bisphosphate and is facilitated by palmitoylation of a single cysteine at position 739 within the large intracellular loop of NCX. The aim of this investigation was to identify the structural determinants of NCX1 palmitoylation. Full-length NCX1 (FL-NCX1) and a YFP fusion protein of the NCX1 large intracellular loop (YFP-NCX1) were expressed in HEK cells. Single amino acid changes around Cys-739 in FL-NCX1 and deletions on the N-terminal side of Cys-739 in YFP-NCX1 did not affect NCX1 palmitoylation, with the exception of the rare human polymorphism S738F, which enhanced FL-NCX1 palmitoylation, and D741A, which modestly reduced it. In contrast, deletion of a 21-amino acid segment enriched in aromatic amino acids on the C-terminal side of Cys-739 abolished YFP-NCX1 palmitoylation. We hypothesized that this segment forms an amphipathic α-helix whose properties facilitate Cys-739 palmitoylation. Introduction of negatively charged amino acids to the hydrophobic face or of helix-breaking prolines impaired palmitoylation of both YFP-NCX1 and FL-NCX1. Alanine mutations on the hydrophilic face of the helix significantly reduced FL-NCX1 palmitoylation. Of note, when the helix-containing segment was introduced adjacent to cysteines that are not normally palmitoylated, they became palmitoylation sites. In conclusion, we have identified an amphipathic α-helix in the NCX1 large intracellular loop that controls NCX1 palmitoylation. NCX1 palmitoylation is governed by a distal secondary structure element rather than by local primary sequence.
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