{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:44:28Z","timestamp":1789184668776,"version":"build-2803163510"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,4,7]]},"abstract":"<jats:p>The nucleocapsid (N-)protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a key role in viral assembly and scaffolding of the viral RNA. It promotes liquid-liquid phase separation (LLPS), forming dense droplets that support the assembly of ribonucleoprotein particles with as-of-yet unknown macromolecular architecture. Combining biophysical experiments, molecular dynamics simulations, and analysis of the mutational landscape, we describe a heretofore unknown oligomerization site that contributes to LLPS, is required for the assembly of higher-order protein-nucleic acid complexes, and is coupled to large-scale conformational changes of N-protein upon nucleic acid binding. The self-association interface is located in a leucine-rich sequence of the intrinsically disordered linker between N-protein folded domains and formed by transient helices assembling into trimeric coiled-coils. Critical residues stabilizing hydrophobic and electrostatic interactions between adjacent helices are highly protected against mutations in viable SARS-CoV-2 genomes, and the oligomerization motif is conserved across related coronaviruses, thus presenting a target for antiviral therapeutics.<\/jats:p>","DOI":"10.1126\/sciadv.adg6473","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T13:58:37Z","timestamp":1680703117000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":61,"title":["A conserved oligomerization domain in the disordered linker of coronavirus nucleocapsid proteins"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-6639","authenticated-orcid":true,"given":"Huaying","family":"Zhao","sequence":"first","affiliation":[{"name":"Laboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3440-1860","authenticated-orcid":true,"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-078X","authenticated-orcid":true,"given":"Sergio A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-3035","authenticated-orcid":true,"given":"Jiji","family":"Chen","sequence":"additional","affiliation":[{"name":"Advanced Imaging and Microscopy Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5270-3678","authenticated-orcid":true,"given":"Grzegorz","family":"Piszczek","sequence":"additional","affiliation":[{"name":"Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8859-6966","authenticated-orcid":true,"given":"Peter","family":"Schuck","sequence":"additional","affiliation":[{"name":"Laboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2031274"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/veac021"},{"key":"e_1_3_3_4_2","first-page":"2022.06.28.4979","article-title":"Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir","author":"Hu Y.","year":"2022","unstructured":"Y.\u00a0Hu, E. M.\u00a0Lewandowski, H.\u00a0Tan, R. T.\u00a0Morgan, X.\u00a0Zhang, M. C.\u00a0Jacobs, S. G.\u00a0Butler, M. V.\u00a0Mongora, J.\u00a0Choy, Y.\u00a0Chen, J.\u00a0Wang, Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. bioRxiv , 2022.06.28.497978 (2022).","journal-title":"bioRxiv"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2739-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.166875"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl6184"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm1208"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010627"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2104241118"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.11.005"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-005-9035-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21953-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167108"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2022.106843"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010121"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19619-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.018"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2019.08.031"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20768-y"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102523"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgac049"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02001-08"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12070929"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102560"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.11.041"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.11.025"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106478"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001351"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001425"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19843-1"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac596"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm4034"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd3629"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.12.009"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.02.074"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.02.069"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0609319"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3909"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.11.016"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06062-w"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi051122c"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.08.026"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501015200"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12104-021-10014-x"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","unstructured":"P. Schuck H.\u00a0Zhao Sedimentation Velocity Analytical Ultracentrifugation: Interacting Systems (CRC Press 2017).","DOI":"10.1201\/b21988"},{"key":"e_1_3_3_47_2","doi-asserted-by":"crossref","first-page":"e4195","DOI":"10.21769\/BioProtoc.4195","article-title":"Measurement of the translational diffusion coefficient and hydrodynamic radius of proteins by dynamic light scattering","volume":"11","author":"Parker E. T.","year":"2021","unstructured":"E. T.\u00a0Parker, P.\u00a0Lollar, Measurement of the translational diffusion coefficient and hydrodynamic radius of proteins by dynamic light scattering. Bio. Protoc. 11, e4195 (2021).","journal-title":"Bio. Protoc."},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202222119"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.202"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1017\/S003358359800345X"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03212-15"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01488-1"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28865-w"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp054042r"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/gch2.1018"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.10.006"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024815118"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1296-1002"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101670R"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.05.018"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56159"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101677"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12091302"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.11.002"},{"key":"e_1_3_3_66_2","doi-asserted-by":"crossref","unstructured":"P. Schuck H.\u00a0Zhao C.\u00a0A.\u00a0Brautigam R.\u00a0Ghirlando Basic Principles of Analytical Ultracentrifugation (CRC Press 2016).","DOI":"10.1201\/b19028"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2015.05.001"},{"key":"e_1_3_3_68_2","doi-asserted-by":"crossref","unstructured":"P. Schuck Sedimentation Velocity Analytical Ultracentrifugation: Discrete Species and Size-Distributions of Macromolecules and Particles (CRC Press 2016).","DOI":"10.1201\/9781315367231"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76630-6"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac302357w"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00713a027"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2346"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty407"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm076"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab631"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adg6473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T16:24:55Z","timestamp":1704817495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adg6473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":76,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2023,4,7]]}},"alternative-id":["10.1126\/sciadv.adg6473"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adg6473","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]},"assertion":[{"value":"2023-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadg6473"}}