A Membrane-Assisted Mechanism for the Release of Ceramide from the CERT START Domain.

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 facili

SUBMITTER: Moqadam M 

PROVIDER: S-EPMC11228987 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature