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PDBsum entry 1c5d
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Immune system
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PDB id
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1c5d
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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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The crystal structure of the FAB fragment of a rat monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor.
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Authors
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M.Kontou,
D.D.Leonidas,
E.H.Vatzaki,
P.Tsantili,
A.Mamalaki,
N.G.Oikonomakos,
K.R.Acharya,
S.J.Tzartos.
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Ref.
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Eur J Biochem, 2000,
267,
2389-2397.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the Fab fragment of a rat monoclonal antibody, number
192, with a very high affinity (Kd = 0.05 nM) for the main immunogenic region of
the human muscle acetylcholine receptor (AChR), has been determined and refined
to 2.4 A resolution by X-ray crystallographic methods. The overall structure is
similar to a Fab (NC6.8) from a murine antibody, used as a search model in
molecular replacement. Structural comparisons with known antibody structures
showed that the conformations of the hypervariable regions H1, H2, L1, L2, L3 of
Fab192 adopt the canonical structures 1, 1, 2, 1, and 1, respectively. The
surface of the antigen-binding site is relatively planar, as expected for an
antibody against a large protein antigen, with an accessible area of 2865 A2.
Analysis of the electrostatic surface potential of the antigen-binding site
shows that the bottom of the cleft formed in the center of the site appears to
be negatively charged. The structure will be useful in the rational design of
very high affinity humanized mutants of Fab192, appropriate for therapeutic
approaches of the model autoimmune disease myasthenia gravis.
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Figure 1.
Fig. 1. Stereo diagrams of residues of the light chain of
Fab192 in the vicinity of the disulphide bond between Cys23 and
Cys88 (a) and residues from the CDR3 loop of the heavy chain (b)
and electron densities from 2Fo-Fc maps. The contour levels
correspond to 0.13 e·Å^-3 (e, electrons). The
figures were produced using the program BOBSCRIPT [43].
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Figure 3.
Fig. 3. A schematic diagram showing the spatial
arrangement of the two molecules of Fab192 in the asymmetric
unit. The first molecule is colored yellow and the second
molecule red. The figure was produced using the program O [20].
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
Eur J Biochem
(2000,
267,
2389-2397)
copyright 2000.
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