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PDBsum entry 5jw3
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Immune system
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PDB id
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5jw3
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Contents |
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316 a.a.
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170 a.a.
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222 a.a.
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206 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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Structure of medi8852 fab fragment in complex with h7 ha
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Structure:
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Hemagglutinin. Chain: a. Fragment: unp residues 19-334. Hemagglutinin. Chain: b. Fragment: unp residues 340-509. Medi8852 heavy chain. Chain: h. Engineered: yes.
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Source:
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Influenza a virus (a/turkey/italy/214845/2002(h7n3)). Organism_taxid: 265120. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t.
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Resolution:
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3.75Å
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R-factor:
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0.227
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R-free:
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0.263
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Authors:
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P.J.Collins,U.Neu,P.A.Walker,M.K.Vorlaender,R.W.Ogrodowicz, S.R.Martin,S.J.Gamblin,J.J.Skehel
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Key ref:
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N.L.Kallewaard
et al.
(2016).
Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.
Cell,
166,
596-608.
PubMed id:
DOI:
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Date:
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11-May-16
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Release date:
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03-Aug-16
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PROCHECK
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Headers
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References
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Q6GYW3
(Q6GYW3_9INFA) -
Hemagglutinin (Fragment) from Influenza A virus
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Seq:
Struc:
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560 a.a.
316 a.a.
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Q6GYW3
(Q6GYW3_9INFA) -
Hemagglutinin (Fragment) from Influenza A virus
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Seq:
Struc:
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560 a.a.
170 a.a.
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DOI no:
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Cell
166:596-608
(2016)
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PubMed id:
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Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.
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N.L.Kallewaard,
D.Corti,
P.J.Collins,
U.Neu,
J.M.McAuliffe,
E.Benjamin,
L.Wachter-Rosati,
F.J.Palmer-Hill,
A.Q.Yuan,
P.A.Walker,
M.K.Vorlaender,
S.Bianchi,
B.Guarino,
A.De Marco,
F.Vanzetta,
G.Agatic,
M.Foglierini,
D.Pinna,
B.Fernandez-Rodriguez,
A.Fruehwirth,
C.Silacci,
R.W.Ogrodowicz,
S.R.Martin,
F.Sallusto,
J.A.Suzich,
A.Lanzavecchia,
Q.Zhu,
S.J.Gamblin,
J.J.Skehel.
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ABSTRACT
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Influenza virus remains a threat because of its ability to evade vaccine-induced
immune responses due to antigenic drift. Here, we describe the isolation,
evolution, and structure of a broad-spectrum human monoclonal antibody (mAb),
MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes.
MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when
compared to other anti-stem antibodies. MEDI8852 is effective in mice and
ferrets with a therapeutic window superior to that of oseltamivir.
Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins
reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly
conserved epitope encompassing a hydrophobic groove in the fusion domain and a
large portion of the fusion peptide, distinguishing it from other structurally
characterized cross-reactive antibodies. The unprecedented breadth and potency
of neutralization by MEDI8852 support its development as immunotherapy for
influenza virus-infected humans.
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