{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:51:25Z","timestamp":1781765485716,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2025-452"],"award-info":[{"award-number":["075-15-2025-452"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly \u03b1-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses.<\/jats:p>","DOI":"10.3390\/ijms27125492","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:52:37Z","timestamp":1781761957000},"page":"5492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Solution Structure of Nucleoprotein Domain 1 from the Emerging Yezo Virus"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7396-3954","authenticated-orcid":false,"given":"Anastasia V.","family":"Gladysheva","sequence":"first","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, 630559 Kol\u2019tsovo, Russia"},{"name":"Physics Department, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey O.","family":"Yanshin","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, 630559 Kol\u2019tsovo, Russia"},{"name":"Physics Department, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9524-9062","authenticated-orcid":false,"given":"Nikita S.","family":"Radchenko","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, 630559 Kol\u2019tsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6942-0840","authenticated-orcid":false,"given":"Irina A.","family":"Osinkina","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, 630559 Kol\u2019tsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor O.","family":"Ukladov","sequence":"additional","affiliation":[{"name":"Scientific Educational Center of the Institute of Chemical Technology, Novosibirsk State University, 630090 Novosibirsk, Russia"},{"name":"Siberian Ring Photon Source \u201cSKIF\u201d, 630559 Kol\u2019tsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2577-0434","authenticated-orcid":false,"given":"Alexander P.","family":"Agafonov","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, 630559 Kol\u2019tsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jiag073","DOI":"10.1093\/infdis\/jiag073","article-title":"Epidemiological, Clinical, and Virological Characterizations of Yezo Virus Infections, an Emerging Tick-borne Orthonairovirus Disease in Japan","volume":"233","author":"Yamaguchi","year":"2026","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Apanasevich, M., Dubovitskiy, N., Derko, A., Khozyainova, A., Tarasov, A., Kokhanenko, A., Artemov, G., Denisov, E., Shestopalov, A., and Sharshov, K. (2025). Genomic Characterization of a Novel Yezo Virus Revealed in Ixodes pavlovskyi Tick Virome in Western Siberia. Viruses, 17.","DOI":"10.3390\/v17101362"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kartashov, M., Svirin, K., Zheleznova, A., Yanshin, A., Radchenko, N., Kurushina, V., Tregubchak, T., Maksimenko, L., Sivay, M., and Ternovoi, V. (2025). First Report of the Yezo Virus Isolates Detection in Russia. Viruses, 17.","DOI":"10.3390\/v17081125"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101363","DOI":"10.1016\/j.onehlt.2026.101363","article-title":"A Novel Orthonairovirus Detected in Grey Seal (Halichoerus grypus)","volume":"22","author":"Leijon","year":"2026","journal-title":"One Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12294","DOI":"10.1128\/JVI.01627-12","article-title":"Structure of Crimean-Congo Hemorrhagic Fever Virus Nucleoprotein: Superhelical Homo-Oligomers and the Role of Caspase-3 Cleavage","volume":"86","author":"Wang","year":"2012","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1074\/jbc.RA118.004976","article-title":"Functional Interaction between Nairovirus N and HSP70\/Related CCHFV Nucleocapsid Protein Research","volume":"294","author":"Jeeva","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yanshin, A.O., Ivkina, D.I., Tuyrin, V.Y., Osinkina, I.A., Tishin, A.E., Olkin, S.E., Ukladov, E.O., Radchenko, N.S., Arkhipov, S.G., and Ryzhykau, Y.L. (2025). Structural Features of Nucleoproteins from the Recently Discovered Orthonairovirus songlingense and Norwavirus beijiense. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157445"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rahman, S., Chiou, C.-C., Almutairi, M.M., Ajmal, A., Batool, S., Javed, B., Tanaka, T., Chen, C.-C., Alouffi, A., and Ali, A. (2024). Targeting Yezo Virus Structural Proteins for Multi-Epitope Vaccine Design Using Immunoinformatics Approach. Viruses, 16.","DOI":"10.3390\/v16091408"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s40203-025-00370-0","article-title":"Molecular Modeling to Design a Multiepitope Vaccine against Emerging Tick-Borne Yezo Virus and Its Validation Through Biophysics Techniques","volume":"13","author":"Hassan","year":"2025","journal-title":"Silico Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5539","DOI":"10.1038\/s41467-021-25857-0","article-title":"A novel nairovirus associated with acute febrile illness in Hokkaido, Japan","volume":"12","author":"Kodama","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_11","first-page":"001974","article-title":"ICTV Virus Taxonomy Profile: Nairoviridae 2024","volume":"105","author":"Kuhn","year":"2024","journal-title":"J. Gen. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e0144624","DOI":"10.1128\/jvi.01446-24","article-title":"Identification of critical residues for RNA binding of nairovirus nucleoprotein","volume":"98","author":"Ohta","year":"2024","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11740","DOI":"10.1128\/JVI.01680-15","article-title":"Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins","volume":"89","author":"Wang","year":"2015","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9305","DOI":"10.1128\/JVI.00661-16","article-title":"Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role in the Nairovirus Replication Cycle","volume":"90","author":"Surtees","year":"2016","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ohta, K., Saka, N., Fukasawa, M., and Nishio, M. (2023). Hazara Orthonairovirus Nucleoprotein Facilitates Viral Cell-to-Cell Spread by Modulating Tight Junction Protein, Claudin-1. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1192956"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Goedhals, D., Paweska, J.T., and Burt, F.J. (2014). Long-Lived CD8+ T Cell Responses Following Crimean-Congo Haemorrhagic Fever Virus Infection. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006149"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.1038\/s41467-024-53362-7","article-title":"Antibodies targeting the Crimean-Congo Hemorrhagic Fever Virus nucleoprotein protect via TRIM21","volume":"15","author":"Leventhal","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/imm.70119","article-title":"Amino Terminal Region of Crimean-Congo Hemorrhagic Fever Virus (CCHFV) Nucleocapsid (NP) Protein Contains Dominant Epitopes Recognised by Cellular Immunity","volume":"178","author":"Pirincal","year":"2026","journal-title":"Immunology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pirincal, A., and Doymaz, M.Z. (2024). The Role of Nucleocapsid Protein (NP) in the Immunology of Crimean\u2013Congo Hemorrhagic Fever Virus (CCHFV). Viruses, 16.","DOI":"10.3390\/v16101547"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez-Rodr\u00edguez, B., Tiede, C., Hoste, A.C.R., Surtees, R.A., Trinh, C.H., Slack, G.S., Chamberlain, J., Hewson, R., Fresco, A., and Sastre, P. (2020). Characterization and Applications of a Crimean-Congo Hemorrhagic Fever Virus Nucleoprotein-Specific Affimer: Inhibitory Effects in Viral Replication and Development of Colorimetric Diagnostic Tests. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008364"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.bpj.2018.01.002","article-title":"HullRad: Fast Calculations of Folded and Disordered Protein and Nucleic Acid Hydrodynamic Properties","volume":"114","author":"Fleming","year":"2018","journal-title":"Biophys. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s41365-020-00825-3","article-title":"BL19U2: Small-Angle X-Ray Scattering Beamline for Biological Macromolecules in Solution at SSRF","volume":"31","author":"Li","year":"2020","journal-title":"Nucl. Sci. Tech."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1107\/S0021889812007662","article-title":"New Developments in the ATSAS Program Package for Small-Angle Scattering Data Analysis","volume":"45","author":"Petoukhov","year":"2012","journal-title":"J. Appl. Crystallogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1093\/bioinformatics\/btx846","article-title":"CHROMIXS: Automatic and Interactive Analysis of Chromatography-Coupled Small-Angle X-Ray Scattering Data","volume":"34","author":"Panjkovich","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1107\/S0021889803012779","article-title":"PRIMUS: A Windows PC-Based System for Small-Angle Scattering Data Analysis","volume":"36","author":"Konarev","year":"2003","journal-title":"J. Appl. Crystallogr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1107\/S0021889892001663","article-title":"Determination of the Regularization Parameter in Indirect-Transform Methods Using Perceptual Criteria","volume":"25","author":"Svergun","year":"1992","journal-title":"J. Appl. Crystallogr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1016\/S0006-3495(99)77443-6","article-title":"Restoring Low Resolution Structure of Biological Macromolecules from Solution Scattering Using Simulated Annealing","volume":"76","author":"Svergun","year":"1999","journal-title":"Biophys. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1107\/S0021889803000268","article-title":"Uniqueness of ab initio Shape Determination in Small-Angle Scattering","volume":"36","author":"Volkov","year":"2003","journal-title":"J. Appl. Crystallogr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1107\/S0021889800014126","article-title":"Automated Matching of High- and Low-Resolution Structural Models","volume":"34","author":"Kozin","year":"2001","journal-title":"J. Appl. Crystallogr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1107\/S0021889895007047","article-title":"CRYSOL\u2014A Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates","volume":"28","author":"Svergun","year":"1995","journal-title":"J. Appl. Crystallogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure Visualization for Researchers, Educators, and Developers","volume":"30","author":"Pettersen","year":"2020","journal-title":"Protein Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"W320","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering key features in protein structures with the new ENDscript server","volume":"42","author":"Robert","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","article-title":"AmberTools","volume":"63","author":"Case","year":"2023","journal-title":"J. Chem. Inf. Model."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:54:57Z","timestamp":1781762097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125492"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125492","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}