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PDBsum entry 2exq
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Immune system
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PDB id
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2exq
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Contents |
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109 a.a.
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115 a.a.
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510 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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Structural model of the mab 806-Egfr complex using computational docking followed by computational and experimental mutagenesis.
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Authors
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A.Sivasubramanian,
G.Chao,
H.M.Pressler,
K.D.Wittrup,
J.J.Gray.
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Ref.
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Structure, 2006,
14,
401-414.
[DOI no: ]
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PubMed id
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Abstract
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In this work, we combined computational protein-protein docking with
computational and experimental mutagenesis to predict the structure of the
complex formed by monoclonal antibody 806 (mAb 806) and the epidermal growth
factor receptor (EGFR). We docked mAb 806, an antitumor antibody, to its epitope
of EGFR residues 287-302. Potential mAb 806-EGFR orientations were generated,
and computational mutagenesis was used to filter them according to their
agreement with experimental mutagenesis data. Further computational mutagenesis
suggested additional mutations, which were tested to arrive at a final structure
that was most consistent with experimental mutagenesis data. We propose that
this is the EGFR-mAb 806 structure, in which mAb 806 binds to an untethered form
of the receptor, consistent with published experimental results. The steric
hindrance created by the antibody near the EGFR dimer interface interferes with
receptor dimerization, and we postulate this as the structural origin for the
antitumor effect of mAb 806.
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Figure 6.
Figure 6. Proposed Structure for the mAb 806-EGFR Complex
(A) Proposed structure for the mAb 806-EGFR complex,
created by structurally aligning model 3 with the hypothetical
extended monomer conformation. The coloring scheme is identical
to that in Figure 5.
(B) Interface interactions: EGFR
residue E293 forms a hydrogen bond with CDR H2 side chain Y50
and makes several hydrophobic contacts, mostly with residues in
the mAb 806 H2 loop.
(C) EGFR residue D297 is well packed
in a pocket of residues from the mAb 806 L2, L3, and H3 CDRs.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2006,
14,
401-414)
copyright 2006.
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