Abstract
A high level of disorder in many viral proteins is a direct consequence of their small genomes, which makes interaction with multiple binding partners a necessity for infection and pathogenicity. A segment of the flaviviral capsid protein (C), also known as the molecular recognition feature (MoRF), undergoes a disorder-to-order transition upon binding to several protein partners. To understand their role in pathogenesis, MoRFs were identified and their occurrence across different flaviviral capsids were studied. Despite lack of sequence similarities, docking studies of Cs with the host proteins indicate conserved interactions involving MoRFs across members of phylogenetic subclades. Additionally, it was observed from the protein–protein networks that some MoRFs preferentially bind proteins that are involved in specialized functions such as ribosome biogenesis. The findings point to the importance of MoRFs in the flaviviral life cycle, with important consequences for disease progression and suppression of the host immune system. Potentially, they might have impacted the way flaviviruses evolved to infect varied hosts using multiple vectors.
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Acknowledgement
SV thanks University Grants Commission-Faculty Recharge Program (UGC-FRP), New Delhi, India, for financial support. The authors thank BIC at DoBT, AU (BT/PR40163/BTIS/137/31/2021), DBT, Govt. of India, for computational facilities.
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AS, PS and PU conceptualized the idea, collected data, carried out analysis, and wrote the paper. KR was involved in interaction and docking studies and drafted the corresponding sections. SV was involved in design of the study, analysis, and review of the manuscript. All authors have reviewed the manuscript before submission.
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Sundar, A., Umashankar, P., Sankar, P. et al. Intrinsic disorder in flaviviral capsid proteins and its role in pathogenesis. J Biosci 49, 57 (2024). https://doi.org/10.1007/s12038-024-00439-6
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DOI: https://doi.org/10.1007/s12038-024-00439-6