spacer
spacer

PDBsum entry 3ixx

Go to PDB code: 
protein links
Virus PDB id
3ixx
Jmol PyMol
Contents
Protein chains
400 a.a.*
80 a.a.* *
221 a.a.* *
213 a.a.* *
* Residue conservation analysis
* C-alpha coords only
PDB id:
3ixx
Name: Virus
Title: The pseudo-atomic structure of west nile immature virus in complex with fab fragments of the anti-fusion loop antibody e53
Structure: Envelope protein e. Chain: a, b, c. Fragment: west nile virus envelope protein. Engineered: yes. Peptide pr. Chain: d, e, f. Fragment: west nile virus pr peptide. Engineered: yes. E53 fab fragment (chain h).
Source: West nile virus. Wnv. Organism_taxid: 11082. Strain: ny99. Mus musculus. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Authors: M.V.Cherrier,B.Kaufmann,G.E.Nybakken,S.M.Lok,J.T.Warren, C.A.Nelson,V.A.Kostyuchenko,H.A.Holdaway,P.R.Chipman, R.J.Kuhn,M.S.Diamond,M.G.Rossmann,D.H.Fremont
Key ref: M.V.Cherrier et al. (2009). Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. EMBO J, 28, 3269-3276. PubMed id: 19713934
Date:
26-Feb-09     Release date:   27-Oct-09    
 Headers
 References

Protein chains
Pfam   ArchSchema ?
A7TZT4  (A7TZT4_WNV) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
3433 a.a.
400 a.a.
Protein chains
Pfam   ArchSchema ?
Q3I100  (Q3I100_WNV) -  Genome polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
3433 a.a.
80 a.a.
Protein chains
No UniProt id for this chain
Struc: 221 a.a.
Protein chains
No UniProt id for this chain
Struc: 213 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     protein dimerization activity     1 term  

 

 
    reference    
 
 
EMBO J 28:3269-3276 (2009)
PubMed id: 19713934  
 
 
Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody.
M.V.Cherrier, B.Kaufmann, G.E.Nybakken, S.M.Lok, J.T.Warren, B.R.Chen, C.A.Nelson, V.A.Kostyuchenko, H.A.Holdaway, P.R.Chipman, R.J.Kuhn, M.S.Diamond, M.G.Rossmann, D.H.Fremont.
 
  ABSTRACT  
 
Flaviviruses are a group of human pathogens causing severe encephalitic or hemorrhagic diseases that include West Nile, dengue and yellow fever viruses. Here, using X-ray crystallography we have defined the structure of the flavivirus cross-reactive antibody E53 that engages the highly conserved fusion loop of the West Nile virus envelope glycoprotein. Using cryo-electron microscopy, we also determined that E53 Fab binds preferentially to spikes in noninfectious, immature flavivirions but is unable to bind significantly to mature virions, consistent with the limited solvent exposure of the epitope. We conclude that the neutralizing impact of E53 and likely similar fusion-loop-specific antibodies depends on its binding to the frequently observed immature component of flavivirus particles. Our results elucidate how fusion-loop antibodies, which comprise a significant fraction of the humoral response against flaviviruses, can function to control infection without appreciably recognizing mature virions. As these highly cross-reactive antibodies are often weakly neutralizing they also may contribute to antibody-dependent enhancement and flavi virus pathogenesis thereby complicating development of safe and effective vaccines.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21388812 I.A.Rodenhuis-Zybert, J.Wilschut, and J.M.Smit (2011).
Partial maturation: an immune-evasion strategy of dengue virus?
  Trends Microbiol, 19, 248-254.  
21264311 Y.Q.Deng, J.X.Dai, G.H.Ji, T.Jiang, H.J.Wang, H.O.Yang, W.L.Tan, R.Liu, M.Yu, B.X.Ge, Q.Y.Zhu, E.D.Qin, Y.J.Guo, and C.F.Qin (2011).
A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein.
  PLoS One, 6, e16059.  
20062797 I.A.Rodenhuis-Zybert, H.M.van der Schaar, J.M.da Silva Voorham, H.van der Ende-Metselaar, H.Y.Lei, J.Wilschut, and J.M.Smit (2010).
Immature dengue virus: a veiled pathogen?
  PLoS Pathog, 6, e1000718.  
20372965 I.A.Rodenhuis-Zybert, J.Wilschut, and J.M.Smit (2010).
Dengue virus life cycle: viral and host factors modulating infectivity.
  Cell Mol Life Sci, 67, 2773-2786.  
20519400 J.Junjhon, T.J.Edwards, U.Utaipat, V.D.Bowman, H.A.Holdaway, W.Zhang, P.Keelapang, C.Puttikhunt, R.Perera, P.R.Chipman, W.Kasinrerk, P.Malasit, R.J.Kuhn, and N.Sittisombut (2010).
Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles.
  J Virol, 84, 8353-8358.  
20592088 S.Sukupolvi-Petty, S.K.Austin, M.Engle, J.D.Brien, K.A.Dowd, K.L.Williams, S.Johnson, R.Rico-Hesse, E.Harris, T.C.Pierson, D.H.Fremont, and M.S.Diamond (2010).
Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2.
  J Virol, 84, 9227-9239.  
20448183 W.Dejnirattisai, A.Jumnainsong, N.Onsirisakul, P.Fitton, S.Vasanawathana, W.Limpitikul, C.Puttikhunt, C.Edwards, T.Duangchinda, S.Supasa, K.Chawansuntati, P.Malasit, J.Mongkolsapaya, and G.Screaton (2010).
Cross-reacting antibodies enhance dengue virus infection in humans.
  Science, 328, 745-748.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.

 

spacer

spacer