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| Title | Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly. |
|---|---|
| Journal, issue, pages | bioRxiv, Year 2024 |
| Publish date | Nov 5, 2024 |
Authors | Mandira Dutta / Kimberly A Dolan / Souad Amiar / Elijah J Bass / Rokaia Sultana / Gregory A Voth / Stephen G Brohawn / Robert V Stahelin / ![]() |
| PubMed Abstract | M is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, M and M, and regulated ...M is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, M and M, and regulated transition between states is hypothesized to coordinate viral assembly and budding. However, the factors that regulate M conformation and roles for each state are unknown. Here, we discover a direct M-sphingolipid interaction that controls M conformational dynamics and virus assembly. We show M binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular dynamics simulations show C1P interaction promotes a long to short transition and energetically stabilizes M. Cryo-EM structures show C1P specifically binds M at a conserved site bridging transmembrane and cytoplasmic regions. Disrupting M-C1P interaction alters M subcellular localization, reduces interaction with Spike and E, and impairs subsequent virus-like particle cell entry. Together, these results show endogenous signaling lipids regulate M structure and support a model in which M is stabilized in the early endomembrane system to organize other structural proteins prior to viral budding. |
External links | bioRxiv / PubMed:39574576 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.01 - 3.03 Å |
| Structure data | EMDB-45919, PDB-9ctu: EMDB-45921, PDB-9ctw: |
| Chemicals | ![]() ChemComp-1PX: ![]() ChemComp-K: |
| Source |
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Keywords | MEMBRANE PROTEIN / SARS-COV-2 / CORONAVIRUS / VIRAL PROTEIN / CAPSID PROTEIN |
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