{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:45Z","timestamp":1785403065038,"version":"3.56.0"},"reference-count":46,"publisher":"International Union of Crystallography (IUCr)","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk?odowska-Curie Actions","doi-asserted-by":"publisher","award":["InnovaXN_8_2020"],"award-info":[{"award-number":["InnovaXN_8_2020"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr F Struct Biol Commun","Acta Crystallogr F","Acta Crystallogr F Struct Biol Cryst Commun","Acta Cryst F","Acta Cryst F Struct Biol Commun","Acta Cryst Sect F","Acta Cryst Sect F Struct Biol Commun","Acta Crystallogr Sect F","Acta Crystallogr Sect F Struct Biol Commun","Acta Crystallogr Sect F Struct Biol Cryst Commun"],"accepted":{"date-parts":[[2026,4,8]]},"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>The papain-like protease (PLpro) of SARS-CoV-2 is part of the multi-domain nonstructural protein 3 (NSP3) and consists of two domains: a ubiquitin-like domain 2 (Ubl2) and a protease domain. PLpro plays a crucial role in the replication cycle of SARS-CoV-2, facilitating host immune-system evasion and the formation of double-membrane vesicles where replication occurs. While the function of the Ubl2 domain is still not clear, it is critical for the stability and the functional efficiency of PLpro. Despite its predicted inherent flexibility, nearly all SARS-CoV-1 and SARS-CoV-2 PLpro crystal structures deposited in the Protein Data Bank show the Ubl2 domain in a highly similar, closed conformation against the catalytic domain. Here, we present a crystal structure of PLpro exhibiting Ubl2 in two distinct conformations: the well characterized closed state, where Ubl2 is positioned near the PLpro domain, and an as yet uncharacterized open state, where Ubl2 is displaced by 4\u2005\u00c5 from the PLpro core. This conformational variability in our structure appears to be related to the occupancy of a zinc ion within the zinc-finger domain. These results provide new insights into the flexibility of Ubl2, suggesting potential avenues for targeting and harnessing this dynamic behaviour for drug discovery.<\/jats:p>","DOI":"10.1107\/s2053230x26003699","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:37:07Z","timestamp":1778161027000},"page":"222-230","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":0,"title":["Structural analysis of the flexibility of the Ubl2 domain within the papain-like protease of SARS-CoV-2"],"prefix":"10.1107","volume":"82","author":[{"given":"Gian Luca","family":"Freiherr von Scholley","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schaefer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039kzrb23","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-9900","authenticated-orcid":true,"given":"Mark D.","family":"Tully","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Andre","family":"Hograindleur","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Soler-L\u00f3pez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-7250","authenticated-orcid":true,"given":"Roman C.","family":"Hillig","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039kzrb23","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Mueller-Dieckmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9877-7621","authenticated-orcid":true,"given":"Eaazhisai","family":"Kandiah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02550n020","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"nq5003_bb1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1107\/S0567739478001618","volume":"34","author":"Agarwal","year":"1978","journal-title":"Acta Cryst. A"},{"key":"nq5003_bb2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1107\/S2059798323003595","volume":"79","author":"Agirre","year":"2023","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13062-025-00690-3","volume":"20","author":"Arya","year":"2025","journal-title":"Biol. Direct"},{"key":"nq5003_bb4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.antiviral.2014.12.015","volume":"115","author":"B\u00e1ez-Santos","year":"2015","journal-title":"Antiviral Res."},{"key":"nq5003_bb5","doi-asserted-by":"crossref","first-page":"34667","DOI":"10.1074\/jbc.M114.609644","volume":"289","author":"Bailey-Elkin","year":"2014","journal-title":"J. Biol. Chem."},{"key":"nq5003_bb6","doi-asserted-by":"crossref","first-page":"15189","DOI":"10.1128\/JVI.79.24.15189-15198.2005","volume":"79","author":"Barretto","year":"2005","journal-title":"J. Virol."},{"key":"nq5003_bb7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fmolb.2020.00174","volume":"7","author":"Bosken","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"nq5003_bb9","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41579-024-01036-y","volume":"22","author":"Chan","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"nq5003_bb10","doi-asserted-by":"crossref","first-page":"104661","DOI":"10.1016\/j.antiviral.2019.104661","volume":"174","author":"Clasman","year":"2020","journal-title":"Antiviral Res."},{"key":"nq5003_bb12","doi-asserted-by":"crossref","unstructured":"Dable-Tupas, G. & Derecho, C. M. P. (2022). Coronavirus Drug Discovery, edited by C. Egbuna, pp. 181-203. Amsterdam: Elsevier.","DOI":"10.1016\/B978-0-323-85156-5.00001-8"},{"key":"nq5003_bb13","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1107\/S1744309107004903","volume":"63","author":"Dimasi","year":"2007","journal-title":"Acta Cryst. F"},{"key":"nq5003_bb14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41392-025-02539-7","volume":"11","author":"Du","year":"2026","journal-title":"Sig. Transduct. Target. Ther."},{"key":"nq5003_bb15","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb16","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1128\/JVI.02220-08","volume":"83","author":"Frieman","year":"2009","journal-title":"J. Virol."},{"key":"nq5003_bb17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.apsb.2020.08.014","volume":"11","author":"Gao","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"nq5003_bb18","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1016\/j.apsb.2025.07.001","volume":"15","author":"Gao","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"nq5003_bb19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41586-024-07817-y","volume":"633","author":"Huang","year":"2024","journal-title":"Nature"},{"key":"nq5003_bb20","unstructured":"Immirzi, A. (1966). Crystallographic Computing Techniques, edited by F. R. Ahmed, p. 399. Copenhagen: Munksgaard."},{"key":"nq5003_bb21","doi-asserted-by":"crossref","first-page":"822785","DOI":"10.3389\/fchem.2022.822785","volume":"10","author":"Jiang","year":"2022","journal-title":"Front. Chem."},{"key":"nq5003_bb22","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1107\/S1600577522007238","volume":"29","author":"Kieffer","year":"2022","journal-title":"J. Synchrotron Rad."},{"key":"nq5003_bb23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ccr.2018.04.009","volume":"367","author":"Kluska","year":"2018","journal-title":"Coord. Chem. Rev."},{"key":"nq5003_bb24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.antiviral.2017.11.001","volume":"149","author":"Lei","year":"2018","journal-title":"Antiviral Res."},{"key":"nq5003_bb25","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb26","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.antiviral.2017.12.015","volume":"150","author":"Lin","year":"2018","journal-title":"Antiviral Res."},{"key":"nq5003_bb27","doi-asserted-by":"crossref","unstructured":"M\u00e1rquez, J. A. & Cipriani, F. (2014). Structural Genomics: General Applications, edited by Y. W. Chen, pp. 197-203. Totowa: Humana Press.","DOI":"10.1007\/978-1-62703-691-7_14"},{"key":"nq5003_bb28","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1107\/S1600577518007166","volume":"25","author":"McCarthy","year":"2018","journal-title":"J. Synchrotron Rad."},{"key":"nq5003_bb29","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1128\/JVI.00338-15","volume":"89","author":"Mielech","year":"2015","journal-title":"J. Virol."},{"key":"nq5003_bb30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13765-023-00842-x","volume":"66","author":"Oktavianawati","year":"2023","journal-title":"Appl. Biol. Chem."},{"key":"nq5003_bb31","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/s41467-021-21060-3","volume":"12","author":"Osipiuk","year":"2021","journal-title":"Nat. Commun."},{"key":"nq5003_bb32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.4149\/gpb_2009_02_174","volume":"28","author":"Pelikan","year":"2009","journal-title":"Gen. Physiol. Biophys."},{"key":"nq5003_bb33","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1107\/S0907444903008126","volume":"59","author":"Potterton","year":"2003","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb34","doi-asserted-by":"crossref","first-page":"5717","DOI":"10.1073\/pnas.0510851103","volume":"103","author":"Ratia","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"nq5003_bb35","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1107\/S002188988800562X","volume":"21","author":"Read","year":"1988","journal-title":"J. Appl. Cryst."},{"key":"nq5003_bb36","doi-asserted-by":"crossref","first-page":"W277","DOI":"10.1093\/nar\/gkaf326","volume":"53","author":"Robert","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"nq5003_bb37","doi-asserted-by":"crossref","first-page":"eabd4596","DOI":"10.1126\/sciadv.abd4596","volume":"6","author":"Rut","year":"2020","journal-title":"Sci. Adv."},{"key":"nq5003_bb38","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/s42003-022-03737-7","volume":"5","author":"Srinivasan","year":"2022","journal-title":"Commun. Biol."},{"key":"nq5003_bb39","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1107\/S0567739473000458","volume":"29","author":"Ten Eyck","year":"1973","journal-title":"Acta Cryst. A"},{"key":"nq5003_bb40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1107\/S1600577522011286","volume":"30","author":"Tully","year":"2023","journal-title":"J. Synchrotron Rad."},{"key":"nq5003_bb41","unstructured":"Tully, M. D., Tarbouriech, N., Rambo, R. P. & Hutin, S. (2021). J. Vis. Exp., e61578."},{"key":"nq5003_bb42","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1107\/S2059798324001487","volume":"80","author":"Vonrhein","year":"2024","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb43","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1107\/S0907444911007773","volume":"67","author":"Vonrhein","year":"2011","journal-title":"Acta Cryst. D"},{"key":"nq5003_bb44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/0889311X.2022.2098281","volume":"28","author":"von Soosten","year":"2022","journal-title":"Crystallogr. Rev."},{"key":"nq5003_bb45","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1126\/science.abd3629","volume":"369","author":"Wolff","year":"2020","journal-title":"Science"},{"key":"nq5003_bb46","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.tim.2020.05.009","volume":"28","author":"Wolff","year":"2020","journal-title":"Trends Microbiol."},{"key":"nq5003_bb50","unstructured":"World Health Organization (2026). COVID-19 Deaths|WHO COVID-19 Dashboard. Geneva: World Health Organization. https:\/\/data.who.int\/dashboards\/covid19\/cases."},{"key":"nq5003_bb47","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s13238-021-00836-9","volume":"12","author":"Zhao","year":"2021","journal-title":"Protein Cell"}],"container-title":["Acta Crystallographica Section F Structural Biology Communications"],"original-title":[],"link":[{"URL":"https:\/\/journals.iucr.org\/f\/issues\/2026\/06\/00\/nq5003\/nq5003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.iucr.org\/f\/issues\/2026\/06\/00\/nq5003\/nq5003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:32:03Z","timestamp":1780317123000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S2053230X26003699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["S2053230X26003699"],"URL":"https:\/\/doi.org\/10.1107\/s2053230x26003699","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1107\/S2053230X26003699\/nq5003sup1.pdf","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb9hhg\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb9hhi\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb9hhh\/pdb","asserted-by":"subject"}]},"ISSN":["2053-230X"],"issn-type":[{"value":"2053-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]},"assertion":[{"value":"Acta Crystallographica Section F: Structural Biology Communications","order":0,"name":"journal","label":"Publication","explanation":{"URL":"https:\/\/journals.iucr.org\/f"},"group":{"name":"general","label":"General"}},{"value":"research communications","order":1,"name":"content_type","label":"Content type","explanation":{"URL":"https:\/\/journals.iucr.org\/f\/services\/notesforauthors.html"},"group":{"name":"general","label":"General"}},{"value":"Available","URL":"https:\/\/scripts.iucr.org\/cgi-bin\/citedin?nq5003","order":2,"name":"article_metrics","label":"Article metrics","group":{"name":"general","label":"General"}},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"12 January 2026","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"8 April 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"18 May 2026","order":2,"name":"published_online","label":"Published online","group":{"name":"publication_history","label":"Publication history"}},{"value":"This article has supporting information","name":"supplementary_materials","label":"Supplementary materials","explanation":{"URL":"https:\/\/scripts.iucr.org\/cgi-bin\/sendsup?nq5003"}},{"value":"\u00a9 2026 Gian Luca Freiherr von Scholley\n                      et al.","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"https:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}},{"value":"Creative Commons Attribution (CC-BY)","order":1,"name":"license","label":"Licence","explanation":{"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}}]}}