文献类型：期刊文献

英文题名：The Intrinsic Disordered N-Terminus of Nucleocapsid Protein of SARS-CoV-2 Is Critical in DNA Aptamer Binding

作者：Lu, Hongye[1];Ma, Jiawen[1];Ma, Xiaomin[2];Wu, Yuanpeng[1];Sun, Xuan[3];Ma, Changxing[1];Li, Xiaoxian[1];Xu, Zhiyong[1];Lu, Pengxi[1];Luo, Zhaofeng[4];Zhang, Liyun[5];Zhang, Lixin[1];Wang, Shenlin[1,6,7]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Sun Yan Sen Univ, Instrumental Anal & Res Ctr, Guangzhou 510006, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Joint Int Res Lab Metab & Dev Sci, Shanghai 200240, Peoples R China;[4]Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China;[5]Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China;[6]Peking Univ, Beijing NMR Ctr, Beijing 100871, Peoples R China;[7]Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China

年份：2026

卷号：27

期号：14

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-105045935620);WOS:【SCI-EXPANDED(收录号:WOS:001832071500001)】；

基金：The work was supported by the National Key R&D Program of China (2024YFA0917100), the National Natural Science Foundation of China (22274050), the Shanghai Science and Technology Commission (contract number: 23J21900300, 24HC2810700), the State Key Laboratory of Medicinal Chemical Biology (Grant No. 2020031), and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：nucleocapsid protein (N protein); DNA aptamer; A48; protein-nucleic acid interaction; intrinsically disordered region (IDR); SARS-CoV-2; NMR

摘要：SARS-CoV-2 nucleocapsid protein (N protein) binds nucleic acids and packages viral RNA. DNA aptamers that specifically bind the N protein have been used in antigen-based COVID-19 detection and have potential clinical applications for preventing SARS-CoV-2 infection. However, the complex structures of the N protein with DNA aptamers and the mechanisms by which aptamers recognize the N protein remain unclear. Here, we report the NMR-derived complex structure of the N-terminal domain of the N protein (N-NTD) with a 58 nt DNA aptamer, A48. The complex structure reveals a distinct topology with a large contact area between A48 and N-NTD. The N-terminal intrinsically disordered region (IDR) of N-NTD forms close contact with A48, primarily stabilized by hydrophilic interactions. Deletion of the N-terminal IDR or substitution of positively charged arginine residues with negatively charged glutamate residues in the IDR region substantially reduced the binding affinity for A48. Because most previously determined N protein structures were obtained using constructs lacking the N-terminal IDR, this study reveals a topology of the N protein-nucleic acid complex and highlights the importance of the N-terminal IDR in nucleic acid binding.