SARS-CoV-2 Spike Protein Post-Translational Modification Landscape and Its Impact on Protein Structure and Function via Computational Prediction

作     者：Buwen Liang Yiying Zhu Wenhao Shi Can Ni Bowen Tan Shaojun Tang Buwen Liang;Yiying Zhu;Wenhao Shi;Can Ni;Bowen Tan;Shaojun Tang

作者机构：The Hong Kong University of Science and Technology(Guangzhou)GuangzhouChina Analysis CenterChemistry DepartmentTsinghua UniversityBeijingChina The Hong Kong University of Science and TechnologyHong Kong SARChina 

出 版 物：《Research》 (研究（英文）)

年 卷 期：2023年第2023卷第3期

页      面：757-767页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：the Guangzhou-HKUST(GZ)Joint Funding Scheme and Guangzhou Municipal Startup Fund 

主　　题：translational substituted overcome 

摘      要：To elucidate the role of post-translational modifications(PTMs)in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike protein’s structure and virulence,we generated a high-resolution map of 87 PTMs using liquid chromatography with tandem mass spectrometry data on the extracted spike protein from SARS-CoV-2 virions and then reconstituted its structure heterogeneity caused by ***,Alphafold2,a high-accuracy artificial intelligence tool to perform protein structure prediction,relies solely on primary amino acid sequence,whereas the impact of PTM,which often modulates critical protein structure and function,is much *** overcome this challenge,we proposed the mutagenesis approach—an in silico,site-directed amino acid substitution to mimic the influence of PTMs on protein structure due to altered physicochemical properties in the post-translationally modified amino acids—and then reconstituted the spike protein’s structure from the substituted sequences by *** the first time,the proposed method revealed predicted protein structures resulting from PTMs,a problem that Alphafold2 has yet to *** an example,we performed computational analyses of the interaction of the post-translationally modified spike protein with its host factors such as angiotensin-converting enzyme 2 to illuminate binding ***,this study suggested the structural analysis of post-translationally modified protein via mutagenesis and deep *** summarize,the reconstructed spike protein structures showed that specific PTMs can be used to modulate host factor binding,guide antibody design,and pave the way for new therapeutic *** code and Supplementary Materials are freely available at https://***/LTZHKUSTGZ/SARS-CoV-2-spike-protein-PTM.