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PDBsum entry 4dqo
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Immune system
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PDB id
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4dqo
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Contents |
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240 a.a.
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214 a.a.
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88 a.a.
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PDB id:
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Immune system
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Title:
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Crystal structure of pg16 fab in complex with v1v2 region from HIV-1 strain zm109
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Structure:
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Pg16 fab heavy chain. Chain: h. Engineered: yes. Pg16 fab light chain. Chain: l. Engineered: yes. 1fd6-v1v2 scaffold zm109 HIV-1 strain. Chain: c. 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: hek293f gnti-. Human immunodeficiency virus 1. Organism_taxid: 11676.
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Resolution:
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2.44Å
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R-factor:
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0.203
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R-free:
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0.230
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Authors:
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M.Pancera,J.S.Mclellan,P.D.Kwong
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Key ref:
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M.Pancera
et al.
(2013).
Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.
Nat Struct Biol,
20,
804-813.
PubMed id:
DOI:
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Date:
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16-Feb-12
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Release date:
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06-Mar-13
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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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Nat Struct Biol
20:804-813
(2013)
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PubMed id:
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Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.
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M.Pancera,
S.Shahzad-Ul-Hussan,
N.A.Doria-Rose,
J.S.McLellan,
R.T.Bailer,
K.Dai,
S.Loesgen,
M.K.Louder,
R.P.Staupe,
Y.Yang,
B.Zhang,
R.Parks,
J.Eudailey,
K.E.Lloyd,
J.Blinn,
S.M.Alam,
B.F.Haynes,
M.N.Amin,
L.X.Wang,
D.R.Burton,
W.C.Koff,
G.J.Nabel,
J.R.Mascola,
C.A.Bewley,
P.D.Kwong.
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ABSTRACT
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HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody.
Select human antibodies, such as the clonally related PG9 and PG16, recognize
glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but
their ability to accommodate diverse glycans is unclear. Here we report the
structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope
comprising both high mannose-type and complex-type N-linked glycans. We combined
structure, NMR and mutagenesis analyses to characterize glycan recognition by
PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine
(RSH), were critical for binding sialic acid on complex-type glycans, and
introduction of these residues into PG9 produced a chimeric antibody with
enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates
evasion, antibody somatic diversity can overcome this and can provide clues to
guide the design of modified antibodies with enhanced neutralization.
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Links
