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PDBsum entry 4zyp
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Immune system
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PDB id
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4zyp
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Contents |
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449 a.a.
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213 a.a.
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211 a.a.
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216 a.a.
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213 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of motavizumab and quaternary-specific rsv- neutralizing human antibody am14 in complex with prefusion rsv f glycoprotein
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Structure:
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Fusion glycoprotein f0,fibritin. Chain: a, b, c. Synonym: protein f. Engineered: yes. Mutation: yes. Motavizumab antibody fab heavy chain. Chain: j, k, n. Engineered: yes. Motavizumab antibody light chain.
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Source:
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Human respiratory syncytial virus a (strain a2), enterobacteria phage t4. Organism_taxid: 11259, 10665. Strain: a2. Gene: wac, t4tp161. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293f. Mus musculus.
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Resolution:
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5.50Å
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R-factor:
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0.214
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R-free:
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0.277
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Authors:
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M.S.A.Gilman,J.S.Mclellan
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Key ref:
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M.S.Gilman
et al.
(2015).
Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
Plos Pathog,
11,
e1005035.
PubMed id:
DOI:
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Date:
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21-May-15
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Release date:
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29-Jul-15
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PROCHECK
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Headers
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References
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D9IEJ2
(D9IEJ2_BPT4) -
Fibritin from Enterobacteria phage T4
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Seq:
Struc:
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487 a.a.
449 a.a.*
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P03420
(FUS_HRSVA) -
Fusion glycoprotein F0 from Human respiratory syncytial virus A (strain A2)
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Seq:
Struc:
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574 a.a.
449 a.a.*
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No UniProt id for this chain
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No UniProt id for this chain
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DOI no:
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Plos Pathog
11:e1005035
(2015)
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PubMed id:
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Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
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M.S.Gilman,
S.M.Moin,
V.Mas,
M.Chen,
N.K.Patel,
K.Kramer,
Q.Zhu,
S.C.Kabeche,
A.Kumar,
C.Palomo,
T.Beaumont,
U.Baxa,
N.D.Ulbrandt,
J.A.Melero,
B.S.Graham,
J.S.McLellan.
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ABSTRACT
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Prevention efforts for respiratory syncytial virus (RSV) have been advanced due
to the recent isolation and characterization of antibodies that specifically
recognize the prefusion conformation of the RSV fusion (F) glycoprotein. These
potently neutralizing antibodies are in clinical development for passive
prophylaxis and have also aided the design of vaccine antigens that display
prefusion-specific epitopes. To date, prefusion-specific antibodies have been
shown to target two antigenic sites on RSV F, but both of these sites are also
present on monomeric forms of F. Here we present a structural and functional
characterization of human antibody AM14, which potently neutralized laboratory
strains and clinical isolates of RSV from both A and B subtypes. The crystal
structure and location of escape mutations revealed that AM14 recognizes a
quaternary epitope that spans two protomers and includes a region that undergoes
extensive conformational changes in the pre- to postfusion F transition. Binding
assays demonstrated that AM14 is unique in its specific recognition of trimeric
furin-cleaved prefusion F, which is the mature form of F on infectious virions.
These results demonstrate that the prefusion F trimer contains potent
neutralizing epitopes not present on monomers and that AM14 should be
particularly useful for characterizing the conformational state of RSV F-based
vaccine antigens.
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