Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37087500.
- Also identified by DOI 10.1038/s41467-023-38047-x and PMC identifier 10122649.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases.
Medical subject headings
- Humans
- Ceramides
- Ceramides/metabolism
- Molecular Dynamics Simulation
- Oxidoreductases
- Oxidoreductases/metabolism
- Membrane Proteins
- Membrane Proteins/genetics
- Membrane Proteins/metabolism