Quantitative Binding Behavior of Intrinsically Disordered Proteins to Nanoparticle Surfaces at Individual Residue Level
Quantitative Binding Behavior of Intrinsically Disordered Proteins to Nanoparticle Surfaces at Individual Residue Level
复制标题
内在无序蛋白质在单个残留水平上与纳米粒子表面的定量结合行为
DOI：
10.1002/chem.201804556
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Brüschweiler, Rafael
中科院分区：
文献类型：
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作者：
Xie, Mouzhe;Li, Da‐Wei;Yuan, Jiaqi;Hansen, Alexandar L.;Brüschweiler, Rafael
定量和预测地了解内在无序蛋白（IDPs）如何与工程纳米颗粒相互作用，对新疗法和纳米毒理学具有潜在的重要意义。基于最近开发的溶液15n核磁共振弛豫方法，从原子细节上报道了四种代表性IDPs与二氧化硅纳米颗粒之间的相互作用。每个IDP具有不同的结合模式，可以用“自由残基相互作用模型”定量解释局部氨基酸残基组成。该模型的参数化使用了游离蛋白氨基酸的结合亲和力以及由位点特异性诱变产生的长期效应，该效应随初级序列的距离呈指数级增长。该模型可通过web服务器访问，可用于预测大量IDPs的残基特异性结合亲和力。
The quantitative and predictive understanding how intrinsically disordered proteins (IDPs) interact with engineered nanoparticles has potentially important implications for new therapeutics as well as nanotoxicology. Based on a recently developed solution15N NMR relaxation approach, the interactions between four representative IDPs with silica nanoparticles are reported at atomic detail. Each IDP possesses distinct binding modes, which can be quantitatively explained by the local amino‐acid residue composition using a “free residue interaction model”. The model was parameterized using the binding affinities of free proteinogenic amino acids along with long‐range effects, derived by site‐specific mutagenesis, that exponentially scale with distance along the primary sequence. The model, which is accessible through a web server, can be applied to predict the residue‐specific binding affinities of a large number of IDPs.