TY  - JOUR
AU  - Krichel, Boris
AU  - Falke, Sven
AU  - Hilgenfeld, Rolf
AU  - Redecke, Lars
AU  - Uetrecht, Charlotte
TI  - Processing of the SARS-CoV pp1a/ab nsp7–10 region
JO  - The biochemical journal / Reviews
VL  - 477
IS  - 5
SN  - 1470-8728
CY  - London [u.a.]
PB  - Portland Pr.8686
M1  - PUBDB-2021-00613
SP  - 1009 - 1019
PY  - 2020
AB  - Severe acute respiratory syndrome coronavirus is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex, essential steps include processing of the conserved polyprotein nsp7–10 region by the main protease M<sup>pro</sup> and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7–10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2 : 2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.
LB  - PUB:(DE-HGF)16
C6  - pmid:32083638
UR  - <Go to ISI:>//WOS:000523312700002
DO  - DOI:10.1042/BCJ20200029
UR  - https://bib-pubdb1.desy.de/record/454611
ER  -