{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:25:52Z","timestamp":1777562752682,"version":"3.51.4"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6,15]]},"abstract":"<jats:p>Dengue is the major arthropod-borne human viral disease, for which no vaccine or specific treatment is available. We used NMR, zeta potential measurements and atomic force microscopy to study the structural features of the interaction between dengue virus C (capsid) protein and LDs (lipid droplets), organelles crucial for infectious particle formation. C protein-binding sites to LD were mapped, revealing a new function for a conserved segment in the N-terminal disordered region and indicating that conformational selection is involved in recognition. The results suggest that the positively charged N-terminal region of C protein prompts the interaction with negatively charged LDs, after which a conformational rearrangement enables the access of the central hydrophobic patch to the LD surface. Taken together, the results allowed the design of a peptide with inhibitory activity of C protein\u2013LD binding, paving the way for new drug development approaches against dengue.<\/jats:p>","DOI":"10.1042\/bj20112219","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T09:17:30Z","timestamp":1332235050000},"page":"405-415","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["The disordered N-terminal region of dengue virus capsid protein contains a lipid-droplet-binding motif"],"prefix":"10.1042","volume":"444","author":[{"given":"Ivo\u00a0C.","family":"Martins","sequence":"first","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal"}]},{"given":"Francisco","family":"Gomes-Neto","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil"},{"name":"Centro Nacional de Resson\u00e2ncia Magn\u00e9tica Nuclear, Universidade Federal do Rio de Janeiro and National Institute of Structural Biology and Bioimage, Rio de Janeiro, RJ, 21941-902, Brazil"}]},{"given":"Andr\u00e9\u00a0F.","family":"Faustino","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal"}]},{"given":"Filomena\u00a0A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal"}]},{"given":"Fabiana\u00a0A.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Polo Avan\u00e7ado de Xer\u00e9m, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ, 25245-390, Brazil"}]},{"given":"Patricia\u00a0T.","family":"Bozza","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil"}]},{"given":"Ronaldo","family":"Mohana-Borges","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Genomica Estrutural, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil"}]},{"given":"Miguel\u00a0A.\u00a0R.\u00a0B.","family":"Castanho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal"}]},{"given":"F\u00e1bio\u00a0C.\u00a0L.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil"},{"name":"Centro Nacional de Resson\u00e2ncia Magn\u00e9tica Nuclear, Universidade Federal do Rio de Janeiro and National Institute of Structural Biology and Bioimage, Rio de Janeiro, RJ, 21941-902, Brazil"}]},{"given":"Nuno\u00a0C.","family":"Santos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal"}]},{"given":"Andrea\u00a0T.","family":"Da\u00a0Poian","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil"}]}],"member":"288","published-online":{"date-parts":[[2012,5,29]]},"reference":[{"key":"2021112215422041500_B1","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.sbi.2008.10.002","article-title":"Function and structure of inherently disordered proteins","volume":"18","author":"Dunker","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2021112215422041500_B2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.pbiomolbio.2010.01.003","article-title":"The protein kingdom extended: ordered and intrinsically disordered proteins, their folding, supramolecular complex formation, and aggregation","volume":"102","author":"Turoverov","year":"2010","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2021112215422041500_B3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tibs.2008.10.009","article-title":"Do viral proteins possess unique biophysical features?","volume":"34","author":"Tokuriki","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"2021112215422041500_B4","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2174\/092986610791498984","article-title":"Viral disorder or disordered viruses: do viral proteins possess unique features?","volume":"17","author":"Xue","year":"2010","journal-title":"Prot. Pept. Lett."},{"key":"2021112215422041500_B5","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.2174\/092986610791498911","article-title":"Intrinsic disorder in the core proteins of flaviviruses","volume":"17","author":"Ivanyi-Nagy","year":"2010","journal-title":"Prot. Pept. Lett."},{"key":"2021112215422041500_B6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrmicro1067","article-title":"A structural perspective of the flavivirus life cycle","volume":"3","author":"Mukhopadhyay","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"2021112215422041500_B7","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1128\/JVI.75.5.2119-2129.2001","article-title":"Self-assembly of nucleocapsid-like particles from recombinant hepatitis C virus core protein","volume":"75","author":"Kunkel","year":"2001","journal-title":"J. Virol."},{"key":"2021112215422041500_B8","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/nar\/gkm1051","article-title":"RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae","volume":"36","author":"Ivanyi-Nagy","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2021112215422041500_B9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1046\/j.1365-2893.2000.00201.x","article-title":"Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes","volume":"7","author":"McLauchlan","year":"2000","journal-title":"J. Viral Hepat."},{"key":"2021112215422041500_B10","doi-asserted-by":"crossref","first-page":"17345","DOI":"10.1073\/pnas.1010811107","article-title":"Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis","volume":"40","author":"Heaton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112215422041500_B11","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.virusres.2009.11.012","article-title":"Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis","volume":"147","author":"Netsawang","year":"2010","journal-title":"Virus Res."},{"key":"2021112215422041500_B12","doi-asserted-by":"crossref","first-page":"e1000632","DOI":"10.1371\/journal.ppat.1000632","article-title":"Dengue virus capsid protein usurps lipid droplets for viral particle formation","volume":"5","author":"Samsa","year":"2009","journal-title":"PLoS Pathog."},{"key":"2021112215422041500_B13","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1096\/fj.09-139469","article-title":"Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection","volume":"24","author":"Assun\u00e7\u00e3o-Miranda","year":"2010","journal-title":"FASEB J."},{"key":"2021112215422041500_B14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11908-010-0102-7","article-title":"Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development","volume":"12","author":"Wilder-Smith","year":"2010","journal-title":"Curr. Infect. Dis. Rep."},{"key":"2021112215422041500_B15","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0092-8674(02)00660-8","article-title":"Structure of dengue virus: implications for flavivirus organization, maturation, and fusion","volume":"108","author":"Kuhn","year":"2002","journal-title":"Cell"},{"key":"2021112215422041500_B16","doi-asserted-by":"crossref","first-page":"7143","DOI":"10.1128\/JVI.77.12.7143-7149.2003","article-title":"Flavivirus capsid is a dimeric \u03b1-helical protein","volume":"77","author":"Jones","year":"2003","journal-title":"J. Virol."},{"key":"2021112215422041500_B17","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1073\/pnas.0305892101","article-title":"Solution structure of dengue virus capsid protein reveals another fold","volume":"101","author":"Ma","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112215422041500_B18","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1128\/JVI.06796-11","article-title":"Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion-dependent and mediated by LD surface proteins","volume":"86","author":"Carvalho","year":"2012","journal-title":"J. Virol."},{"key":"2021112215422041500_B19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: a multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J. Biomol. NMR"},{"key":"2021112215422041500_B20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/BF00404272","article-title":"NMR View: a computer program for the visualization and analysis of NMR data","volume":"4","author":"Johnson","year":"1994","journal-title":"J. Biomol. NMR"},{"key":"2021112215422041500_B21","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/BF02192855","article-title":"Gradient-tailored excitation for single- quantum NMR spectroscopy of aqueous solutions","volume":"2","author":"Piotto","year":"1992","journal-title":"J. Biomol. NMR"},{"key":"2021112215422041500_B22","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2021112215422041500_B23","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1093\/nar\/gkg500","article-title":"Multiple sequence alignment with the Clustal series of programs","volume":"31","author":"Chenna","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2021112215422041500_B24","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera \u2013 a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"2021112215422041500_B25","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.str.2004.04.024","article-title":"West Nile virus core protein; tetramer structure and ribbon formation","volume":"12","author":"Dokland","year":"2004","journal-title":"Structure"},{"key":"2021112215422041500_B26","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis"},{"key":"2021112215422041500_B27","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/psc.1007","article-title":"What can light scattering spectroscopy do for membrane-active peptide studies?","volume":"14","author":"Domingues","year":"2008","journal-title":"J. Pept. Sci."},{"key":"2021112215422041500_B28","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1021\/nn1009648","article-title":"Atomic force microscopy-based molecular recognition of a fibrinogen receptor on human erythrocytes","volume":"4","author":"Carvalho","year":"2010","journal-title":"ACS Nano"},{"key":"2021112215422041500_B29","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1002\/prot.23090","article-title":"Quantitative use of chemical shifts for the modeling of protein complexes","volume":"79","author":"Stratmann","year":"2011","journal-title":"Proteins"},{"key":"2021112215422041500_B30","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.str.2010.11.011","article-title":"Portrayal of complex dynamic properties of sugarcane defensin 5 by NMR: multiple motions associated with membrane interaction","volume":"19","author":"de Paula","year":"2011","journal-title":"Structure"},{"key":"2021112215422041500_B31","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1006\/viro.1997.8608","article-title":"A conserved internal hydrophobic domain mediates the stable membrane integration of the dengue virus capsid protein","volume":"233","author":"Markoff","year":"1997","journal-title":"Virology"},{"key":"2021112215422041500_B32","doi-asserted-by":"crossref","first-page":"14970","DOI":"10.1021\/ja054842f","article-title":"A simple method to predict protein flexibility using secondary chemical shifts","volume":"127","author":"Berjanskii","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"2021112215422041500_B33","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10858-009-9333-z","article-title":"TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts","volume":"44","author":"Shen","year":"2009","journal-title":"J. Biomol. NMR"},{"key":"2021112215422041500_B34","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1432-1033.1986.tb09666.x","article-title":"Sequence-specific 1H-NMR assignments in rabbit-liver metallothionein-2","volume":"157","author":"Wagner","year":"1986","journal-title":"Eur. J. Biochem."},{"key":"2021112215422041500_B35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.tim.2004.02.005","article-title":"Virus yoga: the role of flexibility in virus host cell recognition","volume":"12","author":"Wu","year":"2004","journal-title":"Trends Microbiol."},{"key":"2021112215422041500_B36","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1128\/JVI.02393-07","article-title":"Three-dimensional structure of canine adenovirus serotype 2 capsid","volume":"82","author":"Schoehn","year":"2008","journal-title":"J. Virol."},{"key":"2021112215422041500_B37","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0968-0004(03)00135-X","article-title":"Conformational diversity and protein evolution \u2013 a 60-year-old hypothesis revisited","volume":"28","author":"James","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"2021112215422041500_B38","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.2174\/092986706779026147","article-title":"Implications of protein conformational diversity for binding and development of new biological active compounds","volume":"13","author":"Valente","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"2021112215422041500_B39","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/nature06522","article-title":"Dynamic personalities of proteins","volume":"450","author":"Henzler-Wildman","year":"2007","journal-title":"Nature"},{"key":"2021112215422041500_B40","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/BF01718326","article-title":"RNA binding properties of core protein of the flavivirus Kunjin","volume":"141","author":"Kromykh","year":"1996","journal-title":"Arch. Virol."},{"key":"2021112215422041500_B41","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1099\/vir.0.79775-0","article-title":"The N-terminal half of the core protein of hepatitis C virus is sufficient for nucleocapsid formation","volume":"85","author":"Majeau","year":"2004","journal-title":"J. Gen. Virol."},{"key":"2021112215422041500_B42","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1099\/vir.0.83264-0","article-title":"Multiple regions in dengue virus capsid protein contribute to nuclear localization during virus infection","volume":"89","author":"Sangiambut","year":"2008","journal-title":"J. Gen. Virol."},{"key":"2021112215422041500_B43","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s00705-009-0426-5","article-title":"Production and characterization of anti-dengue capsid antibodies suggesting the N terminus region covering the first 20 amino acids of dengue virus capsid protein is predominantly immunogenic in mice","volume":"154","author":"Puttikhunt","year":"2009","journal-title":"Arch. Virol."},{"key":"2021112215422041500_B44","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1006\/viro.2001.1225","article-title":"Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins","volume":"292","author":"Shi","year":"2002","journal-title":"Virology"},{"key":"2021112215422041500_B45","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1128\/JVI.76.7.3534-3543.2002","article-title":"Capsid protein C of tick-borne encephalitis virus tolerates large internal deletions and is a favorable target for attenuation of virulence","volume":"76","author":"Kofler","year":"2002","journal-title":"J. Virol."},{"key":"2021112215422041500_B46","doi-asserted-by":"crossref","first-page":"5581","DOI":"10.1128\/JVI.02653-08","article-title":"Helices \u03b12 and \u03b13 of West Nile virus capsid protein are dispensable for assembly of infectious virions","volume":"83","author":"Schlick","year":"2009","journal-title":"J. Virol."},{"key":"2021112215422041500_B47","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0022-1759(01)00416-1","article-title":"Use of overlapping peptide mixtures as antigens for cytokine flow cytometry","volume":"255","author":"Maecker","year":"2001","journal-title":"J. Immunol. Meth."},{"key":"2021112215422041500_B48","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1056\/NEJMoa035026","article-title":"Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America","volume":"348","author":"Lalezari","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"2021112215422041500_B49","doi-asserted-by":"crossref","first-page":"11235","DOI":"10.1128\/JVI.01339-10","article-title":"Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance","volume":"84","author":"Welch","year":"2010","journal-title":"J. Virol."},{"key":"2021112215422041500_B50","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1010494","article-title":"Boceprevir for untreated chronic HCV genotype 1 infection","volume":"364","author":"Poordad","year":"2011","journal-title":"N. Engl. J. Med."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/444\/3\/405\/670440\/bj4440405.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/444\/3\/405\/670440\/bj4440405.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T21:55:07Z","timestamp":1637618107000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/444\/3\/405\/46276\/The-disordered-N-terminal-region-of-dengue-virus"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,29]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,6,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20112219","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,29]]}}}