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PDBsum entry 4xaw
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Immune system
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PDB id
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4xaw
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Contents |
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214 a.a.
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215 a.a.
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16 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystallographic identification of lipid as an integral component of the epitope of HIV broadly neutralizing antibody 4e10.
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Authors
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A.Irimia,
A.Sarkar,
R.L.Stanfield,
I.A.Wilson.
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Ref.
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Immunity, 2016,
44,
21-31.
[DOI no: ]
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PubMed id
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Abstract
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Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly
neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane
lipids, but the antibody regions contacting lipids and its orientation with
respect to the viral membrane are unknown. Vaccine immunogens capable of
re-eliciting these membrane proximal external region (MPER)-like antibodies may
require a lipid component to be successful. We performed a systematic
crystallographic study of lipid binding to 4E10 to identify lipids bound by the
antibody and the lipid-interacting regions. We identified phosphatidic acid,
phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the
crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups,
while its CDRH3 interacted with the hydrophobic lipid tails. Identification of
the lipid binding sites on 4E10 may aid design of immunogens for vaccines that
include a lipid component in addition to the MPER on gp41 for generation of
broadly neutralizing antibodies.
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