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PDBsum entry 4zs6
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Immune system
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PDB id
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4zs6
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Contents |
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210 a.a.
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221 a.a.
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207 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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Receptor binding domain and fab complex
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Structure:
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Fab light chain. Chain: l, d. Engineered: yes. Fab heavy chain. Chain: h, c. Engineered: yes. S protein. Chain: a, b. Fragment: receptor binding domain, unp residues 361-589.
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Source:
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Homo sapiens. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293t. Middle east respiratory syndrome coronavirus. Organism_taxid: 1335626. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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3.17Å
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R-factor:
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0.206
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R-free:
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0.245
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Authors:
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X.Yu,X.Wang
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Key ref:
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X.Yu
et al.
(2015).
Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27.
Sci Rep,
5,
13133.
PubMed id:
DOI:
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Date:
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13-May-15
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Release date:
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02-Sep-15
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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DOI no:
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Sci Rep
5:13133
(2015)
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PubMed id:
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Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27.
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X.Yu,
S.Zhang,
L.Jiang,
Y.Cui,
D.Li,
D.Wang,
N.Wang,
L.Fu,
X.Shi,
Z.Li,
L.Zhang,
X.Wang.
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ABSTRACT
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The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV)
causes severe respiratory illness in humans with an approximately 30% mortality
rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates
receptor binding, membrane fusion, and viral entry. We previously reported two
human monoclonal antibodies that target the receptor binding domain (RBD) of the
spike and exhibit strong neutralization activity against live and pesudotyped
MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD
bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The
MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV
receptor DPP4. Further biochemical, viral entry, and neutralization analyses
identified two critical residues in the RBD for both MERS-27 recognition and
DPP4 binding. One of the residues, Trp535, was found to function as an anchor
residue at the binding interface with MERS-27. Upon receptor binding, Trp535
interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits
MERS-CoV infection by directly blocking both protein-protein and
protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results
shed light on the molecular basis of MERS-27 neutralization and will assist in
the optimization of MERS-27 as a tool to combat MERS-CoV infection.
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Links
