tetano
Editor, Senior Moderator
Nature
. 2024 Aug 14.
doi: 10.1038/s41586-024-07817-y. Online ahead of print. Molecular architecture of coronavirus double-membrane vesicle pore complex
Yixin Huang[SUP] 1 [/SUP], Tongyun Wang[SUP] 2 [/SUP], Lijie Zhong[SUP] 1 [/SUP], Wenxin Zhang[SUP] 1 [/SUP], Yu Zhang[SUP] 1 [/SUP], Xiulian Yu[SUP] 3 [/SUP], Shuofeng Yuan[SUP] 4 [/SUP], Tao Ni[SUP] 5 6 [/SUP]
Affiliations
Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications[SUP]1,2[/SUP]. 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[SUP]3-5[/SUP]. 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.
. 2024 Aug 14.
doi: 10.1038/s41586-024-07817-y. Online ahead of print. Molecular architecture of coronavirus double-membrane vesicle pore complex
Yixin Huang[SUP] 1 [/SUP], Tongyun Wang[SUP] 2 [/SUP], Lijie Zhong[SUP] 1 [/SUP], Wenxin Zhang[SUP] 1 [/SUP], Yu Zhang[SUP] 1 [/SUP], Xiulian Yu[SUP] 3 [/SUP], Shuofeng Yuan[SUP] 4 [/SUP], Tao Ni[SUP] 5 6 [/SUP]
Affiliations
- PMID: 39143215
- DOI: 10.1038/s41586-024-07817-y
Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications[SUP]1,2[/SUP]. 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[SUP]3-5[/SUP]. 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.