Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Arch Biochem Biophys. 2020 Apr 15;683:108298. doi: 10.1016/j.abb.2020.108298. Epub 2020 Feb 8.
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.
无规卷曲蛋白区域是生物过程的核心，参与关键的蛋白-配体相互作用。具有重要生物医学意义的病毒，如 Zika 和登革热病毒，其 Flavivirus 蛋白就是很好的例子。这些病毒的几种蛋白都有无规卷曲区域，对于生物活性至关重要。无规卷曲蛋白可以采取几种构象，每种构象都能够与不同的配体相互作用和/或结合。事实上，这种相互作用可以帮助稳定特定的构象。此外，由于它们可以与大量的靶分子结合，这些蛋白区域增加了它们的小蛋白组（10 种蛋白）所能实现的功能数量。无序蛋白的折叠能垒更好地描述了这些蛋白的折叠景观。无规卷曲蛋白可以被认为是沿着折叠能垒滚落，以“下落、折叠和发挥功能”。许多病毒蛋白区域就是这种情况，如 flaviviruses 蛋白组中所见。鉴于它们的体积小，黄病毒是理解无规卷曲蛋白区域在病毒功能中的作用的一个很好的模型系统。最后，研究这些病毒的无规卷曲蛋白区域肯定会有助于针对这些有前景（但具有挑战性）的靶点开发治疗方法。
