Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2.
Name:
Vasiliauskaite et al.pdf
Size:
2.264Mb
Format:
PDF
Description:
Open Access publication
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Vasiliauskaite, IevaOwsianka, Ania
England, Patrick
Khan, Abdul Ghafoor
Cole, Sarah
Bankwitz, Dorothea
Foung, Steven K H
Pietschmann, Thomas
Marcotrigiano, Joseph
Rey, Felix A
Patel, Arvind H
Krey, Thomas
Issue Date
2017-05-16
Metadata
Show full item recordAbstract
The 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.Citation
MBio. 2017 May 16;8(3). pii: mBio.00382-17. doi: 10.1128/mBio.00382-17.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
ASMPubMed ID
28512091Type
ArticleISSN
2150-7511ae974a485f413a2113503eed53cd6c53
10.1128/mBio.00382-17
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International