The dynamic multisite interactions between two intrinsically disordered proteins
KAUST DepartmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Computer Science Program
Computational Bioscience Research Center (CBRC)
Online Publication Date2017-05-24
Print Publication Date2017-06-19
Permanent link to this recordhttp://hdl.handle.net/10754/623649
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AbstractProtein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well characterized folding upon binding to dynamic fuzzy complex. To date, most studies concern the binding of an IDP to a structured protein, while the Interaction between two IDPs is poorly understood. In this study, we combined NMR, smFRET, and molecular dynamics (MD) simulation to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by MD and mutagenesis studies. Our study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.
CitationWu S, Wang D, Liu J, Feng Y, Weng J, et al. (2017) The dynamic multisite interactions between two intrinsically disordered proteins. Angewandte Chemie International Edition. Available: http://dx.doi.org/10.1002/anie.201701883.
SponsorsThis work was supported by National Major Basic Research Program of China (2016YFA0501702), National Science Foundation of China (21473034, 21375028, 21273188), Specialized Research Fund for the Doctoral Program of Higher Education (20130071140004). X. G. and Y. L. thanks the support by funding from King Abdullah University of Science and Technology (KAUST). This research made use of the resources of the computer clusters at KAUST and the computer center at Fudan University.