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PDBsum entry 1p2c
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Immune system/hydrolase
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PDB id
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1p2c
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Contents |
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212 a.a.
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210 a.a.
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129 a.a.
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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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Structural mechanism for affinity maturation of an anti-Lysozyme antibody.
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Authors
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A.Cauerhff,
F.A.Goldbaum,
B.C.Braden.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
3539-3544.
[DOI no: ]
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PubMed id
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Abstract
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In the immune response against a typical T cell-dependent protein antigen, the
affinity maturation process is fast and is associated with the early class
switch from IgM to IgG. As such, a comprehension of the molecular basis of
affinity maturation could be of great importance in biomedical and
biotechnological applications. Affinity maturation of anti-protein antibodies
has been reported to be the result of small structural changes, mostly confined
to the periphery of the antigen-combining site. However, little is understood
about how these small structural changes account for the increase in the
affinity toward the antigen. Herein, we present the three-dimensional structure
of the Fab fragment from BALB/c mouse mAb F10.6.6 in complex with the antigen
lysozyme. This antibody was obtained from a long-term exposure to the antigen.
mAb F10.6.6, and the previously described antibody D44.1, are the result of
identical or nearly identical somatic recombination events. However, different
mutations in the framework and variable regions result in an approximately 10(3)
higher affinity for the F10.6.6 antibody. The comparison of the
three-dimensional structures of these Fab-lysozyme complexes reveals that the
affinity maturation produces a fine tuning of the complementarity of the
antigen-combining site toward the epitope, explaining at the molecular level how
the immune system is able to increase the affinity of an anti-protein antibody
to subnanomolar levels.
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Figure 2.
Fig. 2. Superposition of F10.6.6-HEL (yellow) and D44.1-HEL
(light blue). For clarity, the F[V]-HEL of only one F10.6.6-HEL
and one D44.1-HEL is shown. The superposition identifies no
remarkable conformational differences between F10.6.6 and D44.1;
however, the HEL in the D44.1 complex shows a displacement away
from the antibody, as compared with the F10.6.6-HEL structure.
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Figure 3.
Fig. 3. Stereoview of the CDR L3/HEL interaction in
F10.6.6/HEL (yellow) and D44.1/HEL (light blue) complexes. The
dislocation of the HEL carbonyl by D44.1 CDRL3 Asn is evident.
The average displacement of the HEL C  s in the D44.1-HEL
structures is 0.45 Å.
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Secondary reference #1
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Title
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Lack of significant differences in association rates and affinities of antibodies from short-Term and long-Term responses to hen egg lysozyme.
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Authors
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F.A.Goldbaum,
A.Cauerhff,
C.A.Velikovsky,
A.S.Llera,
M.M.Riottot,
R.J.Poljak.
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Ref.
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J Immunol, 1999,
162,
6040-6045.
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PubMed id
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