金属纳米伴侣界面金属原子对淀粉样蛋白纤维化的调控作用  

Interfacial metal atoms of metallic nano-chaperones on modulating amyloid fibrillation

作　　者：李虎 高冠斌 余良翀 张子俊 张斌 邓昱周 慕庆雪 沈雷 孙涛垒 Hu Li;Guanbin Gao;Liangchong Yu;Zijun Zhang;Bin Zhang;Yuzhou Deng;Qingxue Mu;Lei Shen;Taolei Sun(State Key Laboratory of Advanced Technology for Materials Synthesis and Processing,Wuhan University of Technology,Wuhan 430070,China;Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases,School of Chemistry,Chemical Engineering and Life Science,Wuhan University of Technology,Wuhan 430070,China)

机构地区：[1]State Key Laboratory of Advanced Technology for Materials Synthesis and Processing,Wuhan University of Technology,Wuhan 430070,China [2]Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases,School of Chemistry,Chemical Engineering and Life Science,Wuhan University of Technology,Wuhan 430070,China

出　　处：《Science China Materials》2024年第7期2345-2354,共10页中国科学（材料科学）（英文版）

基　　金：We acknowledge the National Natural Science Foundation of China(52273110,21975191,52372271 and 22173070);the Youth Top Talent Project of Hubei Provence(GGB);the Knowledge Innovation Program of Wuhan-Shuguang Project(GGB);the Fundamental Research Funds for the Central Universities(WUT:2023III013GX)for financial supports.

摘　　要：合成具有生物分子伴侣功能的金属纳米伴侣作为调节蛋白质构象的候选物具有良好的应用前景.尽管对金属纳米伴侣已有广泛研究,但其分子中界面金属原子对蛋白质构象的调控作用及其机制尚不清楚,这严重阻碍了对高性能金属纳米伴侣的开发.本研究以相同配体巯基丙酸(MPA)修饰的金纳米团簇Au_(25)为模型,通过界面掺杂金属原子(Cu、Cd、Ag)精准制备出了三种单原子掺杂的纳米伴侣,分别是Au_(24)Cu_(1)、Au_(24)Cd_(1)和Au_(24)Ag_(1),系统地研究了Au_(25)、Au_(24)Cu_(1)、Au_(24)Cd_(1)和Au_(24)Ag_(1)四种纳米伴侣对Aβ40折叠与纤维化的调控作用.全原子分子动力学模拟结果表明,界面掺杂金属原子(Cu、Cd、Ag)可通过范德华力和静电相互作用等弱相互作用影响与之接触的Aβ40单体的折叠.等温滴定量热分析结果进一步表明,Au_(24)Cu_(1)与Aβ40的相互作用分别是Au_(24)Cd_(1)、Au_(24)Ag_(1)和Au_(25)的1.76、2.09、16.67倍.这些不同的相互作用会导致金属纳米伴侣对Aβ折叠与纤维化的不同调节作用,四种金属纳米伴侣抑制Aβ折叠与纤维化效率依次为Au_(24)Cu1>Au_(24)Cd_(1)>Au_(24)Ag_(1)>Au_(25).本文提供了对金属纳米团簇界面金属原子如何发挥作用的微观分子见解,并为通过操纵界面金属原子来定制金属纳米伴侣提供了基础研究数据.Synthetic metallic nano-chaperones possessing biomolecular chaperone functions hold great promise as candidates for modulating protein conformation.Despite extensive research,the involvement and mechanisms of interfacial metal atoms in metallic nano-chaperones on modulating protein conformation remain elusive,significantly hindering the development of high-performance metallic nano-chaperones.In this study,interfacial atomically precise metal nanoclusters(Au_(25),Au_(24)Ag_(1),Au_(24)Cd_(1),Au_(24)Cu1)modified with the same ligand 3-Mercaptopropionic acid(MPA)were prepared as a model to systematically investigate their modulation effects on Aβ40 fibrillation.All-atom molecular dynamics simulation suggested that the interfacial doped metal atoms(Cu,Cd and Ag)can influence the folding of Aβ40 in contact with them through weak interactions including vander-Waals forces and electrostatic interactions.Isothermal titration calorimetry results further revealed that the interaction of Au_(24)Cu1 to Aβ40 was 1.76,2.09,16.67 times larger than those of Au_(24)Cd_(1),Au_(24)Ag_(1) and Au_(25),respectively.Consequently,these differential interactions translated into different modulating effects of metallic nano-chaperones on Aβfolding and even subsequent fibrillation,with the order of effectiveness being Au_(24)Cu1>Au_(24)Cd_(1)>Au_(24)Ag_(1)>Au_(25).This work provides microscopic molecular insights into the identity of interfacial metal atoms on metallic nanoclusters and offers guidelines for customizing metallic nano-chaperones by manipulating their interfacial metal atoms.

关 键 词：customizing nano-chaperone nano-interface gold-nanoclusters peptide amyloidosis 

分 类 号：Q503[生物学—生物化学] TB383.1[一般工业技术—材料科学与工程]