tetano
Editor, Senior Moderator
Nat Commun
. 2023 Nov 30;14(1):7894.
doi: 10.1038/s41467-023-43666-5. SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle
Liv Zimmermann[SUP] 1 [/SUP], Xiaohan Zhao[SUP] 1 [/SUP], Jana Makroczyova[SUP] 1 [/SUP], Moritz Wachsmuth-Melm[SUP] 1 [/SUP], Vibhu Prasad[SUP] 2 [/SUP], Zach Hensel[SUP] 3 [/SUP], Ralf Bartenschlager[SUP] 2 4 5 [/SUP], Petr Chlanda[SUP] 6 [/SUP]
Affiliations
Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined. Here, we investigate the structure of the DMV pore by in situ cryo-electron tomography combined with subtomogram averaging. We identify non-structural protein (nsp) 3 and 4 as minimal components required for the formation of a DMV-spanning pore, which is dependent on nsp3-4 proteolytic cleavage. In addition, we show that Mac2-Mac3-DPUP-Ubl2 domains are critical for nsp3 oligomerization and crown integrity which influences membrane curvature required for biogenesis of DMVs. Altogether, SARS-CoV-2 nsp3-4 have a dual role by driving the biogenesis of replication organelles and assembly of DMV-spanning pores which we propose here to term replicopores.
. 2023 Nov 30;14(1):7894.
doi: 10.1038/s41467-023-43666-5. SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle
Liv Zimmermann[SUP] 1 [/SUP], Xiaohan Zhao[SUP] 1 [/SUP], Jana Makroczyova[SUP] 1 [/SUP], Moritz Wachsmuth-Melm[SUP] 1 [/SUP], Vibhu Prasad[SUP] 2 [/SUP], Zach Hensel[SUP] 3 [/SUP], Ralf Bartenschlager[SUP] 2 4 5 [/SUP], Petr Chlanda[SUP] 6 [/SUP]
Affiliations
- PMID: 38036567
- DOI: 10.1038/s41467-023-43666-5
Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined. Here, we investigate the structure of the DMV pore by in situ cryo-electron tomography combined with subtomogram averaging. We identify non-structural protein (nsp) 3 and 4 as minimal components required for the formation of a DMV-spanning pore, which is dependent on nsp3-4 proteolytic cleavage. In addition, we show that Mac2-Mac3-DPUP-Ubl2 domains are critical for nsp3 oligomerization and crown integrity which influences membrane curvature required for biogenesis of DMVs. Altogether, SARS-CoV-2 nsp3-4 have a dual role by driving the biogenesis of replication organelles and assembly of DMV-spanning pores which we propose here to term replicopores.