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PDBsum entry 4fqc
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Immune system
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PDB id
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4fqc
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References listed in PDB file
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Key reference
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Title
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Complex-Type n-Glycan recognition by potent broadly neutralizing HIV antibodies.
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Authors
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H.Mouquet,
L.Scharf,
Z.Euler,
Y.Liu,
C.Eden,
J.F.Scheid,
A.Halper-Stromberg,
P.N.Gnanapragasam,
D.I.Spencer,
M.S.Seaman,
H.Schuitemaker,
T.Feizi,
M.C.Nussenzweig,
P.J.Bjorkman.
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Ref.
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Proc Natl Acad Sci U S A, 2012,
109,
E3268.
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PubMed id
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Abstract
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Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent
epitopes on gp120. In contrast to previously characterized glycan-dependent
bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans
in glycan microarrays. We isolated the B-cell clone encoding PGT121, which
segregates into PGT121-like and 10-1074-like groups distinguished by sequence,
binding affinity, carbohydrate recognition, and neutralizing activity. Group
10-1074 exhibits remarkable potency and breadth but no detectable binding to
protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and
their likely germ-line precursor reveal that differential carbohydrate
recognition maps to a cleft between complementarity determining region (CDR)H2
and CDRH3. This cleft was occupied by a complex-type N-glycan in a
"liganded" PGT121 structure. Swapping glycan contact residues between
PGT121 and 10-1074 confirmed their importance for neutralization. Although
PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV
envelopes in isolation and on virions. As HIV envelopes exhibit varying
proportions of high-mannose- and complex-type N-glycans, these results suggest
promiscuous carbohydrate interactions, an advantageous adaptation ensuring
neutralization of all viruses within a given strain.
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