The kinetics of SARS-CoV-2 nsp7-11 polyprotein processing and impact on complexation with nsp16
Schamoni-Kast, K.; Krichel, B.; Damjanovic, T.; Kierspel, T.; Toker, S.; Uetrecht, C.
Show abstract
In severe-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, polyproteins (pp1a/pp1ab) are processed into non-structural proteins (nsps), which largely form the replication/transcription complex (RTC). The polyprotein processing and complex formation is critical and offers potential therapeutic targets. However, the interplay of polyprotein processing and RTC-assembly are poorly understood. Here, we studied two key aspects: The influence of the pp1a terminal nsp11 on the order of polyprotein processing by viral main protease Mpro and the influence of polyprotein processing on core enzyme complex formation. We established a method based on native MS to determine rate constants k considering the structural environment. This enabled us to quantify the multi-reaction kinetics of coronavirus polyprotein processing for the first time. Our results serve as a blueprint for other multi-cleavage reactions. Further, it offers a detailed and quantifiable perspective to the dynamic reactions of SARS-CoV-2 polyprotein processing, which is required for development of novel antivirals.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Mass spectrometry reveals novel features of tubulin polyglutamylation in the flagellum of Trypanosoma brucei 94%
- Median based absolute quantification of proteins using Fully Unlabelled Generic Internal Standard 93%
- In search of the universal method: a comparative survey of bottom-up proteomics sample preparation methods 93%
Similar papers in this journal
- The Whole Proteome, Phosphoproteome, and Glycoproteome Landscape of Pan-Cancer Cell Lines Profiled by Mass Spectrometry and Reverse Phase Protein Array 91%
- Spatial proteomics reveals subcellular reorganization in human keratinocytes exposed to UVA light 90%
- Transcriptomic and proteomic regulation through abundant, dynamic, and independent arginine methylation by Type I and Type II PRMTs 90%
Similar papers in this journal
- N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry 94%
- Towards middle-up analysis of polyclonal antibodies: subclass-specific N-glycosylation profiling of murine immunoglobulin G (IgG) by means of HPLC-MS 91%
- The addition of FAIMS Increases Targeted Proteomics Sensitivity from FFPE Tumor Biopsies 91%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.