Intrinsically disordered protein domains in flavivirus infection

• Published in: Archives of biochemistry and biophysics 2020-04, Vol.683, p.108298-108298, Article 108298
• Main Authors: Martins, Ivo C., Santos, Nuno C.
• Format: Article
• Language: English
• Subjects: Dengue virus (DENV); Flavivirus; Intrinsically disordered protein (IDP); Intrinsically disordered protein regions (IDPRs); Zika virus (ZIKV)
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2020.108298

Intrinsically disordered protein regions are at the core of biological processes and involved in key protein-ligand interactions. The Flavivirus proteins, of viruses of great biomedical importance such as Zika and dengue viruses, exemplify this. Several proteins of these viruses have disordered regions that are of the utmost importance for biological activity. Disordered proteins can adopt several conformations, each able to interact with and/or bind to different ligands. In fact, such interactions can help stabilize a particular fold. Moreover, by being promiscuous in the number of target molecules they can bind to, these protein regions increase the number of functions that their small proteome (10 proteins) can achieve. A folding energy waterfall better describes the protein folding landscape of these proteins. A disordered protein can be thought as rolling down the folding energy cascade, in order “to fall, fold and function”. This is the case of many viral protein regions, as seen in the flaviviruses proteome. Given their small size, flaviviruses are a good model system for understanding the role of intrinsically disordered protein regions in viral function. Finally, studying these viruses disordered protein regions will certainly contribute to the development of therapeutic approaches against such promising (yet challenging) targets. •Intrinsically disordered protein regions (IDPs/IDPRs) are a crucial part of proteomes.•IDPs/IDPRs may have transiently ordered structures, each enabling a specific function.•IDPRs enable multi-functionality, by promoting protein-ligand interactions (PLI).•Viruses, namely flaviviruses, aptly make use of IDPs plasticity & binding promiscuity.•IDPRs ubiquity in PLI makes them a promising (yet challenging) therapeutic target.