Journal Article

PUBDB-2021-00613

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Processing of the SARS-CoV pp1a/ab nsp7–10 region

Krichel, B. ; Falke, S. ; Hilgenfeld, R. ; Redecke, L.EMBL*DESY* ; Uetrecht, C. (Corresponding author)XFEL.EU*

2020
Portland Pr.8686 London [u.a.]

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Please use a persistent id in citations: doi:10.1042/BCJ20200029  doi:10.3204/PUBDB-2021-00613

Abstract: 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$^{pro}$ 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.

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Contributing Institute(s):

1. FS-Photon Science (FS-PS)
2. DOOR-User (DOOR ; HAS-User)
3. Universität zu Lübeck (U Lübeck)

Research Program(s):

1. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)
2. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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