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-Structure paper
| タイトル | Molecular architecture of coronavirus double-membrane vesicle pore complex. |
|---|---|
| ジャーナル・号・ページ | Nature, Vol. 633, Issue 8028, Page 224-231, Year 2024 |
| 掲載日 | 2024年8月14日 |
著者 | Yixin Huang / Tongyun Wang / Lijie Zhong / Wenxin Zhang / Yu Zhang / Xiulian Yu / Shuofeng Yuan / Tao Ni / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:39143215 / PubMed Central |
| 手法 | EM (サブトモグラム平均) |
| 解像度 | 4.2 - 6.2 Å |
| 構造データ | EMDB-39107, PDB-8yax: EMDB-39109, PDB-8yb5: ![]() EMDB-39111: SARS-CoV-2 DMV nsp3-4 pore complex (extended-pore) EMDB-39112, PDB-8yb7: ![]() EMDB-39113: SARS-CoV-2 DMV nsp3-4 pore complex (mini-pore) ![]() EMDB-39159: SARS-CoV-2 DMV nsp3-4 pore complex (full-length-pore) |
| 由来 |
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キーワード | VIRAL PROTEIN / Double membrane vesicle / pore complex / nsp3 / nsp4 / RNA transport |
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