9CTU
Cryo-EM structure of SARS-CoV-2 M (short conformation)bound to C1P
Summary for 9CTU
| Entry DOI | 10.2210/pdb9ctu/pdb |
| EMDB information | 45919 |
| Descriptor | short conformation Fab light chain, short conformation Fab heavy chain, Membrane protein, ... (5 entities in total) |
| Functional Keywords | sars-cov-2, coronavirus, viral protein, capsid protein, membrane protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 6 |
| Total formula weight | 161696.34 |
| Authors | Dolan, K.A.,Brohawn, S.G. (deposition date: 2024-07-25, release date: 2024-11-06, Last modification date: 2024-12-11) |
| Primary citation | Dutta, M.,Dolan, K.A.,Amiar, S.,Bass, E.J.,Sultana, R.,Voth, G.A.,Brohawn, S.G.,Stahelin, R.V. Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly. Biorxiv, 2024 Cited by 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 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. PubMed: 39574576DOI: 10.1101/2024.11.04.620124 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.03 Å) |
Structure validation
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