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PDBsum entry 3w9e
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Viral protein/immune system
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PDB id
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3w9e
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Contents |
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229 a.a.
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215 a.a.
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211 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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Structure of human monoclonal antibody e317 fab complex with hsv-2 gd
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Structure:
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Envelope glycoprotein d. Chain: c. Fragment: unp residues 1-300. Synonym: gd. Engineered: yes. Antibody fab heavy chain. Chain: a. Engineered: yes. Antibody fab light chain.
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Source:
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Human herpesvirus 2. Hhv-2. Organism_taxid: 10315. Strain: hg52. Gene: gd. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293. Homo sapiens.
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Resolution:
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2.30Å
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R-factor:
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0.206
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R-free:
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0.255
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Authors:
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C.C.Lee,L.L.Lin,A.H.J.Wang
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Key ref:
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C.C.Lee
et al.
(2013).
Structural basis for the antibody neutralization of herpes simplex virus.
Acta Crystallogr D Biol Crystallogr,
69,
1935-1945.
PubMed id:
DOI:
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Date:
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03-Apr-13
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Release date:
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02-Oct-13
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PROCHECK
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Headers
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References
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Q69467
(GD_HHV2H) -
Envelope glycoprotein D from Human herpesvirus 2 (strain HG52)
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Seq:
Struc:
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393 a.a.
229 a.a.
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DOI no:
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Acta Crystallogr D Biol Crystallogr
69:1935-1945
(2013)
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PubMed id:
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Structural basis for the antibody neutralization of herpes simplex virus.
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C.C.Lee,
L.L.Lin,
W.E.Chan,
T.P.Ko,
J.S.Lai,
A.H.Wang.
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ABSTRACT
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Glycoprotein D (gD) of herpes simplex virus (HSV) binds to a host cell surface
receptor, which is required to trigger membrane fusion for virion entry into the
host cell. gD has become a validated anti-HSV target for therapeutic antibody
development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was
previously raised against HSV gD for viral neutralization. To understand the
structural basis of antibody neutralization, crystals of the gD ectodomain bound
to the E317 Fab domain were obtained. The structure of the complex reveals that
E317 interacts with gD mainly through the heavy chain, which covers a large area
for epitope recognition on gD, with a flexible N-terminal and C-terminal
conformation. The epitope core structure maps to the external surface of gD,
corresponding to the binding sites of two receptors, herpesvirus entry mediator
(HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the
gD-nectin-1 interface and occludes the HVEM contact site of gD to block its
binding to either receptor. The binding of E317 to gD also prohibits the
formation of the N-terminal hairpin of gD for HVEM recognition. The major
E317-binding site on gD overlaps with either the nectin-1-binding residues or
the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and
Phe223). The epitopes of gD for E317 binding are highly conserved between two
types of human herpesvirus (HSV-1 and HSV-2). This study enables the
virus-neutralizing epitopes to be correlated with the receptor-binding regions.
The results further strengthen the previously demonstrated therapeutic and
diagnostic potential of the E317 antibody.
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Links
