ArticleThe journal of physical chemistry. B2024
A Membrane-Assisted Mechanism for the Release of Ceramide from the CERT START Domain.
Article in The journal of physical chemistry. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Article
- Exploring Ceramide C16:0 as a Novel Biomarker and Therapeutic Target for Atherosclerosis.Journal of the American Heart Association · 2026Review
- Getting a grip on StAR-related lipid-transfer (START) domain proteins in bacteria.FEMS microbiology reviews · 2026Review
- Coordination of transporter, cargo, and membrane properties during non-vesicular lipid transport.Communications biology · 2024Article
- Model Mechanism for Lipid Uptake by the Human STARD2/PC-TP Phosphatidylcholine Transfer Protein.The journal of physical chemistry letters · 2024Article
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Authors and funding
7 authors.
Funding
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Abstract
Ceramide transfer protein CERT is the mediator of nonvesicular transfer of ceramide from the ER to Golgi. In CERT, START is the domain responsible for the binding and transport of ceramide. A wealth of structural data has revealed a helix-grip fold surrounding a large hydrophobic cavity holding the ceramide. Yet, little is known about the mechanisms by which START releases the ceramide through the polar region and into the packed environment of cellular membranes. As such events do not lend themselves easily to experimental investigations, we used multiple unbiased microsecond-long molecular simulations. We propose a membrane-assisted mechanism in which the membrane acts as an allosteric effector initiating the release of ceramide and where the passage of the ceramide acyl chains is facilitated by the intercalation of a single phosphatidylcholine lipid in the cavity, practically greasing the ceramide way out. We verify using free energy calculation and experimental lipidomics data that CERT forms stable complexes with phosphatidylcholine lipids, in addition to ceramide, thus providing validation for the proposed mechanism.
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Registered trials
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