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PDBsum entry 5aea
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Cell adhesion
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PDB id
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5aea
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References listed in PDB file
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Key reference
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Title
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I-Bodies, Human single domain antibodies that antagonize chemokine receptor cxcr4.
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Authors
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K.Griffiths,
O.Dolezal,
B.Cao,
S.K.Nilsson,
H.B.See,
K.D.Pfleger,
M.Roche,
P.R.Gorry,
A.Pow,
K.Viduka,
K.Lim,
B.G.Lu,
D.H.Chang,
T.Murray-Rust,
M.Kvansakul,
M.A.Perugini,
C.Dogovski,
M.Doerflinger,
Y.Zhang,
K.Parisi,
J.L.Casey,
S.D.Nuttall,
M.Foley.
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Ref.
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J Biol Chem, 2016,
291,
12641-12657.
[DOI no: ]
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PubMed id
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Abstract
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CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic
target for a range of clinical conditions, including stem cell mobilization,
cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report
here the development of a fully human single-domain antibody-like scaffold
termed an "i-body," the engineering of which produces an i-body
library possessing a long complementarity determining region binding loop, and
the isolation and characterization of a panel of i-bodies with activity against
human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range
of in vitro and in vivo assays, including inhibition of HIV infection, cell
migration, and leukocyte recruitment but, importantly, not the mobilization of
hematopoietic stem cells. Epitope mapping of the three CXCR4 i-bodies AM3-114,
AM4-272, and AM3-523 revealed binding deep in the binding pocket of the receptor.
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