{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:54:19Z","timestamp":1791276859247,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2024YFA0917100"],"award-info":[{"award-number":["2024YFA0917100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22274050"],"award-info":[{"award-number":["22274050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["22274050"],"award-info":[{"award-number":["22274050"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["23J21900300"],"award-info":[{"award-number":["23J21900300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["24HC2810700"],"award-info":[{"award-number":["24HC2810700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011408","name":"State Key Laboratory of Medicinal Chemical Biology","doi-asserted-by":"crossref","award":["2020031"],"award-info":[{"award-number":["2020031"]}],"id":[{"id":"10.13039\/501100011408","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2020031"],"award-info":[{"award-number":["2020031"]}],"id":[{"id":"https:\/\/ror.org\/032p70522","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms27146386","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:32:54Z","timestamp":1784539974000},"page":"6386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Intrinsic Disordered N-Terminus of Nucleocapsid Protein of SARS-CoV-2 Is Critical in DNA Aptamer Binding"],"prefix":"10.3390","volume":"27","author":[{"given":"Hongye","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0458-5132","authenticated-orcid":false,"given":"Xiaomin","family":"Ma","sequence":"additional","affiliation":[{"name":"Instrumental Analysis and Research Center, Sun Yan-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanpeng","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-2637","authenticated-orcid":false,"given":"Xuan","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxing","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengxi","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-8204","authenticated-orcid":false,"given":"Zhaofeng","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-0578","authenticated-orcid":false,"given":"Shenlin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"},{"name":"Beijing NMR Center and College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41467-020-20768-y","article-title":"The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein","volume":"12","author":"Lu","year":"2021","journal-title":"Nat. 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