SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle

Autor: Liv Zimmermann, Xiaohan Zhao, Jana Makroczyova, Moritz Wachsmuth-Melm, Vibhu Prasad, Zach Hensel, Ralf Bartenschlager, Petr Chlanda
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-43666-5
Popis: Abstract 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.
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