Electrostatic and hydrophobic interaction cooperative nanochaperone regulates protein folding  

作　　者：Xiaohui Wu Fei Deng Yujie Chen Mengchen Xu Feihe Ma Linqi Shi 

机构地区：[1]Key Laboratory of Functional Polymer Materials of Ministry of Education,State Key Laboratory of Medicinal Chemical Biology,Institute of Polymer Chemistry and College of Chemistry,Nankai University,Tianjin,P.R.China [2]School of Materials Science and Engineering and State Key Laboratory of Separation Membranes and Membrane Processes,Tiangong University,Tianjin,P.R.China

出　　处：《Aggregate》2024年第1期419-426,共8页聚集体（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:51933006,52373153,52293383;National Key Research and Development Program of China,Grant/Award Number:2022YFA1205702;Haihe Laboratory of Sustainable Chemical Transformations,Grant/Award Number:YYJC202102。

摘　　要：Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding.However,synthesis of such molecules is a big challenge.The concept of“aggregate science”provides insights to construct chemical entities(aggregates)beyond molecular levels to mimic both the structure and function of natural chaperone.Inspired by this concept,herein we fabricate a novel multi-interaction(i.e.,electrostatic and hydrophobic interaction)cooperative nanochaperone(multi-co-nChap)to regulating protein folding.This multi-co-nChap is fabricated by rationally introducing electrostatic interactions to the surface(corona)and confined hydrophobic microdomains(shell)of traditional single-hydrophobic interaction nanochaperone.We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains,while the shell electrostatic interaction balances the capture and release of clients.By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction,the optimized multi-co-nChap effectively facilitated de novo folding of nascent polypeptides.Moreover,the synergy between corona electrostatic attraction,shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi-co-nChap to protect native proteins from denaturation at harsh temperatures.This work provides important insights for understanding and design of nanochaperone,which is a kind of ordered aggregate with chaperone-like activity that beyond the level of single molecule.

关 键 词：chaperone-like activity cooperative effect nanochaperones ordered aggregates protein folding 

分 类 号：TB383[一般工业技术—材料科学与工程]