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dc.contributor.authorVasiliauskaite, Ieva
dc.contributor.authorOwsianka, Ania
dc.contributor.authorEngland, Patrick
dc.contributor.authorKhan, Abdul Ghafoor
dc.contributor.authorCole, Sarah
dc.contributor.authorBankwitz, Dorothea
dc.contributor.authorFoung, Steven K H
dc.contributor.authorPietschmann, Thomas
dc.contributor.authorMarcotrigiano, Joseph
dc.contributor.authorRey, Felix A
dc.contributor.authorPatel, Arvind H
dc.contributor.authorKrey, Thomas
dc.date.accessioned2019-01-16T09:27:48Z
dc.date.available2019-01-16T09:27:48Z
dc.date.issued2017-05-16
dc.identifier.citationMBio. 2017 May 16;8(3). pii: mBio.00382-17. doi: 10.1128/mBio.00382-17.en_US
dc.identifier.issn2150-7511
dc.identifier.pmid28512091
dc.identifier.doi10.1128/mBio.00382-17
dc.identifier.urihttp://hdl.handle.net/10033/621652
dc.description.abstractThe hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design.en_US
dc.publisherASMen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCD81 binding siteen_US
dc.subjectIg-like domainen_US
dc.subjectconformational flexibilityen_US
dc.subjectglycoprotein E2en_US
dc.subjecthepatitis C virusen_US
dc.subjectmonoclonal antibodiesen_US
dc.subjectvaccine designen_US
dc.titleConformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
refterms.dateFOA2019-01-16T09:27:49Z
dc.source.journaltitlemBio


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