ArticleNature2012
Molecular recognition of a single sphingolipid species by a protein's transmembrane domain.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 2 of them syntheses that pooled it.
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Who cites it
167 citing papers in PubMed, 2 syntheses or guidelines pooled it, 371 citations in OpenAlex.
- TMED family genes and their roles in human diseases.International journal of medical sciences · 2023Pooled it
- An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.Scientific reports · 2019Pooled it
- The ER-Golgi intermediate compartment: a central hub integrating membrane trafficking and stress responses.EMBO reports · 2026Review
- Sphingolipid Metabolism Links Morphological Signatures to Immunomodulatory Potency in Human Mesenchymal Stromal Cells.Cellular and molecular bioengineering · 2026Article
- Lipid-trap mass spectrometry identifies lipid-protein interactions in cells.Nature cell biology · 2026Article
- Ceramide disrupts TM9SF2-PGK1 axis to redirect PD-L1 trafficking and enhance antitumor immunity.Nature communications · 2026Article
- Living at the border: biophysical gateways into membrane protein insertion and folding.Biophysical reviews · 2026Review
- Beyond Vesicular Traffic: The ERES as the Gateway for Biosynthetic Secretion.Sub-cellular biochemistry · 2026Review
- Lipid Metabolism and Trafficking in the Golgi Apparatus.Sub-cellular biochemistry · 2026Review
- St. John's Wort for Depression: From Neurotransmitters to Membrane Plasticity.International journal of molecular sciences · 2025Review
- Impact of Nutrition on Sphingolipid-Regulated Physiology: A Review.Molecular nutrition & food research · 2025Review
- Optical Control of Membrane Viscosity Modulates ER-to-Golgi Trafficking.ACS central science · 2025Article
- The Involvement of Glycerophospholipids in Susceptibility of Maize to Gibberella Root Rot Revealed by Comparative Metabolomics and Mass Spectrometry Imaging Joint Analysis.Plants (Basel, Switzerland) · 2025Article
- Comprehensive Identification of Lipid-Membrane Protein Interactions via Advanced Proteomics and Extended Lipid-Immobilized Bead Technology.Analytical chemistry · 2025Article
- TMED9 coordinates the clearance of misfolded GPI-anchored proteins out of the ER and into the Golgi.PLoS biology · 2025Article
- ER-to-Golgi trafficking through a dynamic intermediate cis-Golgi tubular network in Arabidopsis.Nature cell biology · 2025Article
- The role and regulatory mechanism of lysosome associated protein transmembrane 4β in tumors.Frontiers in oncology · 2025Review
- Imaging Plant Lipids with Fluorescent Reporters.Plants (Basel, Switzerland) · 2024Review
- How ceramides affect the development of colon cancer: from normal colon to carcinoma.Pflugers Archiv : European journal of physiology · 2024Review
- A NiNature communications · 2024Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
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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.