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PDBsum entry 4zpw
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Viral protein
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PDB id
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4zpw
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PDB id:
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| Name: |
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Viral protein
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Title:
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Structure of unbound mers-cov spike receptor-binding domain (england1 strain).
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Structure:
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Spike glycoprotein. Chain: r, s. Fragment: receptor-binding domain, unp residues 381-588. Synonym: s glycoprotein,e2,peplomer protein. Engineered: yes
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Source:
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Human coronavirus emc (isolate united kingdom/h123990006/2012). Hcov-emc. Organism_taxid: 1263720. Strain: isolate united kingdom/h123990006/2012. Gene: s, 3. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293.
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Resolution:
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3.02Å
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R-factor:
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0.220
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R-free:
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0.259
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Authors:
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M.G.Joyce,J.R.Mascola,B.S.Graham,P.D.Kwong
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Key ref:
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L.Wang
et al.
(2015).
Evaluation of candidate vaccine approaches for MERS-CoV.
Nat Commun,
6,
7712.
PubMed id:
DOI:
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Date:
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08-May-15
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Release date:
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12-Aug-15
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PROCHECK
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Headers
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References
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K9N5Q8
(SPIKE_CVEMC) -
Spike glycoprotein from Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
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Seq:
Struc:
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1353 a.a.
208 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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DOI no:
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Nat Commun
6:7712
(2015)
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PubMed id:
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Evaluation of candidate vaccine approaches for MERS-CoV.
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L.Wang,
W.Shi,
M.G.Joyce,
K.Modjarrad,
Y.Zhang,
K.Leung,
C.R.Lees,
T.Zhou,
H.M.Yassine,
M.Kanekiyo,
Z.Y.Yang,
X.Chen,
M.M.Becker,
M.Freeman,
L.Vogel,
J.C.Johnson,
G.Olinger,
J.P.Todd,
U.Bagci,
J.Solomon,
D.J.Mollura,
L.Hensley,
P.Jahrling,
M.R.Denison,
S.S.Rao,
K.Subbarao,
P.D.Kwong,
J.R.Mascola,
W.P.Kong,
B.S.Graham.
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ABSTRACT
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The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a
cause of severe respiratory disease highlights the need for effective approaches
to CoV vaccine development. Efforts focused solely on the receptor-binding
domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing
antibody (NAb) responses. Here we show that immunogens based on full-length S
DNA and S1 subunit protein elicit robust serum-neutralizing activity against
several MERS-CoV strains in mice and non-human primates. Serological analysis
and isolation of murine monoclonal antibodies revealed that immunization elicits
NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization
mechanisms were demonstrated by solving the atomic structure of a NAb-RBD
complex, through sequencing of neutralization escape viruses and by constructing
MERS-CoV S variants for serological assays. Immunization of rhesus macaques
confers protection against MERS-CoV-induced radiographic pneumonia, as assessed
using computerized tomography, supporting this strategy as a promising approach
for MERS-CoV vaccine development.
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Links
