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The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins
Author(s) -
Wu Shaowen,
Wang Dongdong,
Liu Jin,
Feng Yitao,
Weng Jingwei,
Li Yu,
Gao Xin,
Liu Jianwei,
Wang Wenning
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201701883
Subject(s) - intrinsically disordered proteins , molecular dynamics , computational biology , folding (dsp implementation) , biophysics , ctd , chemistry , biology , computational chemistry , electrical engineering , oceanography , engineering , geology
Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well‐characterized folding upon binding to dynamic fuzzy complexes. 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, NMR, smFRET, and molecular dynamics (MD) simulation are combined 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 molecular dynamics and mutagenesis studies. This 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.