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PDBsum entry 4xi5
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Viral protein/immune system
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PDB id
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4xi5
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Contents |
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728 a.a.
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132 a.a.
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206 a.a.
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208 a.a.
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PDB id:
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| Name: |
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Viral protein/immune system
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Title:
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Ghgl of varicella-zoster virus in complex with human neutralizing antibodies
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Structure:
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Envelope glycoprotein h. Chain: a. Synonym: gh,glycoprotein iii,gpiii. Engineered: yes. Envelope glycoprotein l. Chain: b. Synonym: gl. Engineered: yes. Fab-94 light chain.
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Source:
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Human herpesvirus 3 strain oka vaccine. Hhv-3. Organism_taxid: 341980. Gene: gh, orf37. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: gl, orf60. Homo sapiens. Organism_taxid: 9606.
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Resolution:
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3.90Å
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R-factor:
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0.247
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R-free:
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0.276
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Authors:
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Y.Xing
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Key ref:
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Y.Xing
et al.
(2015).
A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.
Proc Natl Acad Sci U S A,
112,
6056-6061.
PubMed id:
DOI:
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Date:
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06-Jan-15
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Release date:
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13-May-15
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PROCHECK
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Headers
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References
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Q775J3
(GH_VZVO) -
Envelope glycoprotein H from Varicella-zoster virus (strain Oka vaccine)
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Seq:
Struc:
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841 a.a.
728 a.a.
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Q9J3N1
(GL_VZVO) -
Envelope glycoprotein L from Varicella-zoster virus (strain Oka vaccine)
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Seq:
Struc:
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160 a.a.
132 a.a.
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DOI no:
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Proc Natl Acad Sci U S A
112:6056-6061
(2015)
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PubMed id:
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A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.
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Y.Xing,
S.L.Oliver,
T.Nguyen,
C.Ciferri,
A.Nandi,
J.Hickman,
C.Giovani,
E.Yang,
G.Palladino,
C.Grose,
Y.Uematsu,
A.E.Lilja,
A.M.Arvin,
A.Carfí.
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ABSTRACT
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Varicella-zoster virus (VZV), of the family Alphaherpesvirinae, causes varicella
in children and young adults, potentially leading to herpes zoster later in life
on reactivation from latency. The conserved herpesvirus glycoprotein gB and the
heterodimer gHgL mediate virion envelope fusion with cell membranes during virus
entry. Naturally occurring neutralizing antibodies against herpesviruses target
these entry proteins. To determine the molecular basis for VZV neutralization,
crystal structures of gHgL were determined in complex with fragments of antigen
binding (Fabs) from two human monoclonal antibodies, IgG-94 and IgG-RC, isolated
from seropositive subjects. These structures reveal that the antibodies target
the same site, composed of residues from both gH and gL, distinct from two other
neutralizing epitopes identified by negative-stain electron microscopy and
mutational analysis. Inhibition of gB/gHgL-mediated membrane fusion and
structural comparisons with herpesvirus homologs suggest that the IgG-RC/94
epitope is in proximity to the site on VZV gHgL that activates gB. Immunization
studies proved that the anti-gHgL IgG-RC/94 epitope is a critical target for
antibodies that neutralize VZV. Thus, the gHgL/Fab structures delineate a site
of herpesvirus vulnerability targeted by natural immunity.
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