磷酸化调控蛋白质结合 z-bo 2020-11-02 466

　　Recently, Duan Mojie, an associate researcher of the theoretical and computational chemistry group of the Institute of Precision Measurement Science and Technology Innovation of the Chinese Academy of Sciences, and others used computational simulation methods and enhanced sampling techniques to reveal the effect of phosphorylation on the inherent disordered KID structure and the process of binding to KIX protein. Regulation mechanism.

　　phosphorylation modification is a common post-translational modification in organisms, and it plays an important role in the regulation of signal transduction, cell growth and apoptosis. More phosphorylation sites are located on inherently disordered proteins or regions of disordered proteins. The highly dynamic and stretch properties of these proteins make them easier to be chemically modified. At the same time, post-translational modifications such as phosphorylation can change and regulate the structure and function of inherently disordered proteins. As a model system, the kinase-inducing domain KID, after being phosphorylated, binds to the KIX domain on the transcriptional coactivator protein CBP and regulates the expression of target genes. Due to the highly dynamic nature of the inherently disordered protein structure, there is still a lack of reasonable explanations on how phosphorylation modification at a single site can efficiently regulate the molecular mechanism of KID and KIX binding.

　　Molecular dynamics simulation uses theoretical calculation methods to observe and obtain protein structure changes at the atomic level. In order to obtain the structure change of KID and the process of combining with KIX, the researchers used enhanced sampling technology to obtain the free energy change of the process of combining KID-KIX. The results show that the changes in charge distribution and electrostatic interactions on proteins caused by phosphorylation are not the direct cause of the changes in binding capacity. After phosphorylation, a hydrophobic cluster (HRC) composed of hydrophobic residues is formed on the pKID protein. Its high hydrophobicity drives the interaction between KID and the aromatic residue tyrosine on KIX, and further guides pKID to complete the binding And the folding process. This study reveals the molecular mechanism of KID and KIX binding, and provides new ideas for phosphorylation modification to regulate the structure and function of proteins.