Potential toxicity mechanism of MoS2 nanotube in the interaction between YAP65 WW domain and PRM
Potential toxicity mechanism of MoS2 nanotube in the interaction between YAP65 WW domain and PRM
复制标题
MoS2纳米管在YAP65 WW结构域与PRM相互作用中的潜在毒性机制
DOI：
10.1016/j.colsurfb.2020.111317
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Cuiling Ren
中科院分区：
文献类型：
--
作者：
Yajie Meng;Ruirui Liu;Min Zhu;Honglin Zhai;Cuiling Ren
随着二硫化钼（MoS2）在生物医学中的广泛应用，其与生物分子的作用机制越来越受到人们的关注。本文通过分子动力学模拟研究了mos2纳米管对信号蛋白YAP65结合的影响，YAP65是一个重要的Yes激酶相关蛋白结构域（WW结构域）与脯氨酸基序配体（PRM）结合。我们基于WW结构域、PRM和mos2纳米管之间不同的初始结合模式设计了四种体系，并观察了两种方式对WW结构域与PRM结合的影响。第一种途径是，mos2纳米管占据WW结构域的活性位点，阻止WW结构域与PRM结合。在第二种途径中，WW结构域与PRM结合的残基是W17和F29，而不是两个高度保守的残基（Y28和W39），形成了不稳定的组合。这两种结果都可能导致WW域失去原有功能或传递错误信号。然而，mos2纳米管并没有破坏复合材料中WW域和PRM的结构和结合。这些发现揭示了mos2纳米管与信号蛋白系统之间的相互作用，同时为mos2纳米管的潜在纳米毒性提供了另一种有价值的见解。
With the widespread application of Molybdenum disulfide (MoS2) in biomedicine, its mechanism of action with biomolecules has attracted increasing attention. Herein, molecular dynamics simulations were performed to investigate the effect of MoS2nanotube on the binding of the signal protein YAP65, an important Yes kinase-associated protein domain (WW domain), to the proline rich motif ligand (PRM). We designed four systems based on the different initial binding modes among WW domain, PRM and MoS2nanotube, and observed two ways to affect the binding of WW domain to PRM. The first pathway, the active site in WW domain was occupied by MoS2nanotube, which prevents WW domain from binding to PRM. In the second pathway, WW domain was bound to PRM with residues W17 and F29 instead of the two highly conserved residues (Y28 and W39), forming an unstable combination. These two results might cause WW domain to lose its original function or to pass the mistaken signal. However, MoS2nanotube did not destroy the structure and binding of WW domain and PRM in the composite. These findings shed light on the interaction between MoS2nanotube and signal protein system, while providing another valuable insight into the potential nanotoxicity of MoS2nanotube.