8YAX
SARS-CoV-2 DMV nsp3-4 pore complex (full-pore)
Summary for 8YAX
| Entry DOI | 10.2210/pdb8yax/pdb |
| EMDB information | 39107 |
| Descriptor | Papain-like protease nsp3, Non-structural protein 4 (2 entities in total) |
| Functional Keywords | double membrane vesicle, pore complex, nsp3, nsp4, rna transport, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 4 |
| Total formula weight | 547401.54 |
| Authors | Huang, Y.X.,Zhong, L.J.,Zhang, W.X.,Ni, T. (deposition date: 2024-02-10, release date: 2024-06-19, Last modification date: 2024-11-06) |
| Primary citation | Huang, Y.,Wang, T.,Zhong, L.,Zhang, W.,Zhang, Y.,Yu, X.,Yuan, S.,Ni, T. Molecular architecture of coronavirus double-membrane vesicle pore complex. Nature, 633:224-231, 2024 Cited by PubMed Abstract: Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications. SARS-CoV-2 non-structural protein 3 (nsp3) and nsp4 are the minimal viral components required to induce DMV formation and to form a double-membrane-spanning pore, essential for the transport of newly synthesized viral RNAs. The mechanism of DMV pore complex formation remains unknown. Here we describe the molecular architecture of the SARS-CoV-2 nsp3-nsp4 pore complex, as resolved by cryogenic electron tomography and subtomogram averaging in isolated DMVs. The structures uncover an unexpected stoichiometry and topology of the nsp3-nsp4 pore complex comprising 12 copies each of nsp3 and nsp4, organized in 4 concentric stacking hexamer rings, mimicking a miniature nuclear pore complex. The transmembrane domains are interdigitated to create a high local curvature at the double-membrane junction, coupling double-membrane reorganization with pore formation. The ectodomains form extensive contacts in a pseudo-12-fold symmetry, belting the pore complex from the intermembrane space. A central positively charged ring of arginine residues coordinates the putative RNA translocation, essential for virus replication. Our work establishes a framework for understanding DMV pore formation and RNA translocation, providing a structural basis for the development of new antiviral strategies to combat coronavirus infection. PubMed: 39143215DOI: 10.1038/s41586-024-07817-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.9 Å) |
Structure validation
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