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PDBsum entry 4hkb
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Immune system
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PDB id
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4hkb
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Contents |
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(+ 0 more)
218 a.a.
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193 a.a.
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164 a.a.
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179 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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Ch67 fab (unbound) from the ch65-67 lineage
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Structure:
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Ch67 heavy chain. Chain: j, a, c, e, g, i. Fragment: fab. Engineered: yes. Ch67 light chain. Chain: n, b, d, f, h, k. Fragment: fab. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293. Expression_system_cell_line: hek 293
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Resolution:
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3.60Å
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R-factor:
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0.261
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R-free:
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0.306
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Authors:
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A.G.Schmidt,S.C.Harrison
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Key ref:
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A.G.Schmidt
et al.
(2013).
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.
Proc Natl Acad Sci U S A,
110,
264-269.
PubMed id:
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Date:
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15-Oct-12
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Release date:
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21-Nov-12
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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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No UniProt id for this chain
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Proc Natl Acad Sci U S A
110:264-269
(2013)
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PubMed id:
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Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.
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A.G.Schmidt,
H.Xu,
A.R.Khan,
T.O'Donnell,
S.Khurana,
L.R.King,
J.Manischewitz,
H.Golding,
P.Suphaphiphat,
A.Carfi,
E.C.Settembre,
P.R.Dormitzer,
T.B.Kepler,
R.Zhang,
M.A.Moody,
B.F.Haynes,
H.X.Liao,
D.E.Shaw,
S.C.Harrison.
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ABSTRACT
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Affinity maturation refines a naive B-cell response by selecting mutations in
antibody variable domains that enhance antigen binding. We describe a B-cell
lineage expressing broadly neutralizing influenza virus antibodies derived from
a subject immunized with the 2007 trivalent vaccine. The lineage comprises three
mature antibodies, the unmutated common ancestor, and a common intermediate.
Their heavy-chain complementarity determining region inserts into the conserved
receptor-binding pocket of influenza HA. We show by analysis of structures,
binding kinetics and long time-scale molecular dynamics simulations that
antibody evolution in this lineage has rigidified the initially flexible
heavy-chain complementarity determining region by two nearly independent
pathways and that this preconfiguration accounts for most of the affinity gain.
The results advance our understanding of strategies for developing more broadly
effective influenza vaccines.
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Links
