Record Details

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

DIR@IMTECH: CSIR-Institute of Microbial Technology

View Archive Info
 
 
Field Value
 
Title Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes
 
Creator Bhardwaj, Taniya
Gadhave, Kundlik
Kapuganti, Shivani K
Kumar, Prateek
Brotzakis, Z.F
Saumya, Kumar Udit
Nayak, Namyashree
Kumar, Ankur
Joshi , Richa
Mukherjee, Bodhidipra
Bhardwaj, Aparna
Thakur, Krishan Gopal
Garg, Neha
Vendruscolo, Michele
Giri, Rajanish
 
Subject QR Microbiology
 
Description The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in 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 (APRs) in these proteomes and revealed a strong aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV and SARS-CoV-2 proteins and protein regions, including the signal sequence peptide and fusion peptides 1 and 2 of the spike protein, a peptide from the NSP6 protein, and the ORF10 and NSP11 proteins. Our results show that these peptides and proteins can form amyloid aggregates. We used circular dichroism spectroscopy to reveal the presence of β-sheet rich cores in aggregates and X-ray diffraction and Raman spectroscopy to confirm the formation of amyloid structures. Furthermore, we demonstrated that SARS-CoV-2 NSP11 aggregates are toxic to mammalian cell cultures. These results motivate further studies about the possible role of aggregation of SARS proteins in protein misfolding diseases and other human conditions.
 
Publisher Nature Pub. Group
 
Date 2023-02-20
 
Type Article
PeerReviewed
 
Relation https://www.nature.com/articles/s41467-023-36234-4
http://crdd.osdd.net/open/3166/
 
Identifier Bhardwaj, Taniya and Gadhave, Kundlik and Kapuganti, Shivani K and Kumar, Prateek and Brotzakis, Z.F and Saumya, Kumar Udit and Nayak, Namyashree and Kumar, Ankur and Joshi , Richa and Mukherjee, Bodhidipra and Bhardwaj, Aparna and Thakur, Krishan Gopal and Garg, Neha and Vendruscolo, Michele and Giri, Rajanish (2023) Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes. Nature communications, 14 (1). ISSN 2041-1723