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PDBsum entry 1oay
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Immune system
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PDB id
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1oay
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Contents |
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121 a.a.
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108 a.a.
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85 a.a.
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92 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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Antibody multispecificity mediated by conformational diversity.
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Authors
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L.C.James,
P.Roversi,
D.S.Tawfik.
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Ref.
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Science, 2003,
299,
1362-1367.
[DOI no: ]
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PubMed id
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Abstract
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A single antibody was shown to adopt different binding-site conformations and
thereby bind unrelated antigens. Analysis by both x-ray crystallography and
pre-steady-state kinetics revealed an equilibrium between different preexisting
isomers, one of which possessed a promiscuous, low-affinity binding site for
aromatic ligands, including the immunizing hapten. A subsequent induced-fit
isomerization led to high-affinity complexes with a deep and narrow binding
site. A protein antigen identified by repertoire selection made use of an
unrelated antibody isomer with a wide, shallow binding site. Conformational
diversity, whereby one sequence adopts multiple structures and multiple
functions, can increase the effective size of the antibody repertoire but may
also lead to autoimmunity and allergy.
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Figure 1.
Fig. 1. The four different isomers of IgE antibody SPE7. A
close-up view of the binding site is shown as a semitransparent
surface, colored according to electrostatic potential (blue for
positive, red for negative). The figure was prepared with GRASP
(39, 40) and AESOP (41). The Ab^3 and Ab^4 models are presented
without ligand.
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Figure 2.
Fig. 2. Details of SPE7's binding site and main-chain
superposition of isomers. (A to C) Hapten-bound SPE7 with (A)
DNP-Ser, (B) Az, and (C) Fur. Putative hydrogen bonds are
indicated by dotted spheres between acceptor and donor atoms.
(D) Main-chain configurations of free isomers Ab^1 (green) and
Ab^2 (purple), hapten-bound isomer Ab^3 (blue), and
Trx-Shear3-bound isomer Ab^4 (ochre). All figures were prepared
with SETOR (41).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
299,
1362-1367)
copyright 2003.
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