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PDBsum entry 12e8
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Immunoglobulin
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PDB id
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12e8
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Contents |
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* Residue conservation analysis
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DOI no:
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Acta Crystallogr D Biol Crystallogr
55:122-128
(1999)
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PubMed id:
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Structure of a monoclonal 2E8 Fab antibody fragment specific for the low-density lipoprotein-receptor binding region of apolipoprotein E refined at 1.9 A.
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S.Trakhanov,
S.Parkin,
R.Raffaï,
R.Milne,
Y.M.Newhouse,
K.H.Weisgraber,
B.Rupp.
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ABSTRACT
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The crystal structure of the Fab fragment of 2E8, the monoclonal IgG1,kappa
antibody specific for the low-density lipoprotein (LDL) receptor-binding region
of apolipoprotein E (apoE), has been solved by molecular replacement and refined
at 1.9 A resolution (PDB entry 12E8). Two 2E8 Fab molecules in the asymmetric
unit are related by noncrystallographic symmetry and are hydrogen bonded through
a beta-sheet-like intermolecular contact between the heavy-chain
complementarity-determining regions 3 (CDRH3) of each molecule. The structure
has been refined to an R value of 0.22 (Rfree = 0.27). The initially ill-defined
heavy-chain constant domain (CH1) of 2E8 has been retraced with the aid of
automatic refinement, confirming the beta-sheet tracing independently of any
starting models. As a resolution better than 2 A is not common for Fab
fragments, this model represents a well defined Fab structure and should prove
useful in MR solution of other Fab fragments. Furthermore, in the absence of an
LDL-receptor structure, the homology of the 2E8 CDRH2 to the ligand-binding
domain of the LDL receptor has been exploited to model the apoE-LDL-receptor
interaction.
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Selected figure(s)
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Figure 1.
Figure 1 Native Patterson map created by XtalView (McRee,
1992[McRee, D. E. (1992). J. Mol. Graph. 10, 44-46.]) showing
the strong Harker peak indicative of an NCS axis parallel to the
crystallographic 2[1] screw axis.
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Figure 4.
Figure 4 Ribbon representation of the topology of the 2E8 Fab
dimer. The two light chains (C[L] and V[L]) are red and yellow,
respectively, and the two heavy chains (C[H1] and V[H]) are blue
and green, respectively. The dimer interface is formed by the
complementarity-determining regions. The figure was created with
MOLSCRIPT (Kraulis, 1991[Kraulis, P. J. (1991). J. Appl. Cryst.
24, 946-950.]).
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(1999,
55,
122-128)
copyright 1999.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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Google scholar
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PubMed id
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Reference
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A.Honegger,
A.D.Malebranche,
D.Röthlisberger,
and
A.Plückthun
(2009).
The influence of the framework core residues on the biophysical properties of immunoglobulin heavy chain variable domains.
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Protein Eng Des Sel,
22,
121-134.
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B.W.Segelke,
M.Forstner,
M.Knapp,
S.D.Trakhanov,
S.Parkin,
Y.M.Newhouse,
H.D.Bellamy,
K.H.Weisgraber,
and
B.Rupp
(2000).
Conformational flexibility in the apolipoprotein E amino-terminal domain structure determined from three new crystal forms: implications for lipid binding.
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Protein Sci,
9,
886-897.
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PDB codes:
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R.Raffaï,
K.H.Weisgraber,
R.MacKenzie,
B.Rupp,
E.Rassart,
T.Hirama,
T.L.Innerarity,
and
R.Milne
(2000).
Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling.
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J Biol Chem,
275,
7109-7116.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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