Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes

The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge on the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a pane...

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Bibliographic Details
Published in:bioRxiv 2021-06
Main Authors: Bhardwaj, Taniya, Gadhave, Kundlik, Kapuganti, Shivani Krishna, Kumar, Prateek, Zacharias Faidon Brotzakis, Kumar Udit Saumya, Nayak, Namyashree, Kumar, Ankur, Garg, Neha, Vendruscolo, Michele, Giri, Rajanish
Format: Article
Language:English
Subjects:
Aggregation behavior
Amyloidogenesis
NSP6 protein
Peptides
Protein interaction
Protein sorting signals
Proteins
Proteomes
Severe acute respiratory syndrome coronavirus 2
Spike protein
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Summary:The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge on the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions in these proteomes, and revealed an enhanced aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV-2 proteins, including the signal sequence peptide and fusion peptide 1 of the spike protein, a peptide from the NSP6 protein (NSP6-p), the ORF10 protein, and the NSP11 protein. Our results show that these peptides and proteins form aggregates via a nucleation-dependent mechanism. Moreover, we demonstrated that the aggregates of NSP11 are toxic to mammalian cell cultures. These findings provide evidence about the aggregation of proteins in the SARS-CoV-2 proteome. Competing Interest Statement The authors have declared no competing interest. Footnotes * We have now systematically revised the writing of the manuscript. Also added a significance paragraph.
DOI:10.1101/2021.05.29.446267