4JVP

Three dimensional structure of broadly neutralizing anti - Hepatitis C virus (HCV) glycoprotein E2 alpaca nanobody D03


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission.

Tarr, A.W.Lafaye, P.Meredith, L.Damier-Piolle, L.Urbanowicz, R.A.Meola, A.Jestin, J.L.Brown, R.J.McKeating, J.A.Rey, F.A.Ball, J.K.Krey, T.

(2013) Hepatology 58: 932-939

  • DOI: https://doi.org/10.1002/hep.26430
  • Primary Citation of Related Structures:  
    4JVP

  • PubMed Abstract: 

    Severe liver disease caused by chronic hepatitis C virus is the major indication for liver transplantation. Despite recent advances in antiviral therapy, drug toxicity and unwanted side effects render effective treatment in liver-transplanted patients a challenging task. Virus-specific therapeutic antibodies are generally safe and well-tolerated, but their potential in preventing and treating hepatitis C virus (HCV) infection has not yet been realized due to a variety of issues, not least high production costs and virus variability. Heavy-chain antibodies or nanobodies, produced by camelids, represent an exciting antiviral approach; they can target novel highly conserved epitopes that are inaccessible to normal antibodies, and they are also easy to manipulate and produce. We isolated four distinct nanobodies from a phage-display library generated from an alpaca immunized with HCV E2 glycoprotein. One of them, nanobody D03, recognized a novel epitope overlapping with the epitopes of several broadly neutralizing human monoclonal antibodies. Its crystal structure revealed a long complementarity determining region (CD3) folding over part of the framework that, in conventional antibodies, forms the interface between heavy and light chain. D03 neutralized a panel of retroviral particles pseudotyped with HCV glycoproteins from six genotypes and authentic cell culture-derived particles by interfering with the E2-CD81 interaction. In contrast to some of the most broadly neutralizing human anti-E2 monoclonal antibodies, D03 efficiently inhibited HCV cell-to-cell transmission.


  • Organizational Affiliation

    School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Anti-HCV E2 alpaca nanobody D03
A, B
143Vicugna pacosMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.183 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.806α = 90
b = 52.806β = 90
c = 182.471γ = 120
Software Package:
Software NamePurpose
XDSdata scaling
PHASERphasing
BUSTERrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-24
    Type: Initial release
  • Version 1.1: 2013-10-23
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description