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PDBsum entry 1dn2
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Immune system
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PDB id
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1dn2
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Convergent solutions to binding at a protein-Protein interface.
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Authors
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W.L.Delano,
M.H.Ultsch,
A.M.De vos,
J.A.Wells.
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Ref.
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Science, 2000,
287,
1279-1283.
[DOI no: ]
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PubMed id
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Abstract
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The hinge region on the Fc fragment of human immunoglobulin G interacts with at
least four different natural protein scaffolds that bind at a common site
between the C(H2) and C(H3) domains. This "consensus" site was also
dominant for binding of random peptides selected in vitro for high affinity
(dissociation constant, about 25 nanomolar) by bacteriophage display. Thus, this
site appears to be preferred owing to its intrinsic physiochemical properties,
and not for biological function alone. A 2.7 angstrom crystal structure of a
selected 13-amino acid peptide in complex with Fc demonstrated that the peptide
adopts a compact structure radically different from that of the other Fc binding
proteins. Nevertheless, the specific Fc binding interactions of the peptide
strongly mimic those of the other proteins. Juxtaposition of the available
Fc-complex crystal structures showed that the convergent binding surface is
highly accessible, adaptive, and hydrophobic and contains relatively few sites
for polar interactions. These are all properties that may promote cross-reactive
binding, which is common to protein-protein interactions and especially
hormone-receptor complexes.
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Figure 2.
Fig. 2. Crystal structure of Fc-III (DCAWHLGELVWCT-NH[2]), in
complex with IgG-Fc. (A) Ribbon diagrams of two Fc-III peptides
in complex with the Fc dimer; (B) close-up view of the peptide
interacting with the surface of IgG-Fc. This structure has been
deposited in the PDB under accession number 1DN2.
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Figure 3.
Fig. 3. Molecular surface representation of the consensus
binding site on IgG-Fc [coordinates from Deisenhofer (3)]. (A)
Fc with superimposed binding interfaces of Protein A, Protein G,
and rheumatoid factor. (The 4.5 Å crystal structure of the
Fc-receptor/Fc complex was excluded because of its low
resolution.) Atoms are colored blue, yellow, or red depending on
whether they are involved in one, two, or three of the
interfaces, respectively (17). (B) As in (A) with the interface
of the Fc binding peptide (Fc-III) superimposed in green. Fc-III
interacts with many of the atoms that are found in the
interfaces of the other three Fc binding proteins.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2000,
287,
1279-1283)
copyright 2000.
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