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PDBsum entry 2orb
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Immune system
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PDB id
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2orb
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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 structure of the anti-C-Myc antibody 9e10 FAB fragment/epitope peptide complex reveals a novel binding mode dominated by the heavy chain hypervariable loops.
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Authors
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N.Krauss,
H.Wessner,
K.Welfle,
H.Welfle,
C.Scholz,
M.Seifert,
K.Zubow,
J.Aÿ,
M.Hahn,
P.Scheerer,
A.Skerra,
W.Höhne.
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Ref.
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Proteins, 2008,
73,
552-565.
[DOI no: ]
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PubMed id
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Abstract
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The X-ray structure of the Fab fragment from the anti-c-myc antibody 9E10 was
determined both as complex with its epitope peptide and for the free Fab. In the
complex, two Fab molecules adopt an unusual head to head orientation with the
epitope peptide arranged between them. In contrast, the free Fab forms a dimer
with different orientation. In the Fab/peptide complex the peptide is bound to
one of the two Fabs at the "back" of its extended CDR H3, in a cleft with CDR
H1, thus forming a short, three-stranded antiparallel beta-sheet. The N- and
C-terminal parts of the peptide are also in contact with the neighboring Fab
fragment. Comparison between the CDR H3s of the two Fab molecules in complex
with the peptide and those from the free Fab reveals high flexibility of this
loop. This structural feature is in line with thermodynamic data from isothermic
titration calorimetry.
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Figure 2.
Figure 2. Superposition of antibody 9E10 C[  ]traces
(variable domains) in stereo representation. (A) The epitope
peptide complex for Fab(a) (V[L]: blue; V[H]: yellow; epitope
peptide: red sticks) and Fab(b) (V[L]: light blue; V[H]:
orange). Only the framework C[ ]coordinates
were used for superposition, yielding an rmsd of 0.92 Å.
(B) Fab(a) from the complex (light chain: blue; heavy chain
fragment: yellow; epitope peptide: red sticks) and free Fab(a)
(light chain: light blue; heavy chain fragment: orange, rmsd
0.45 Å for framework C[ ]positions).
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Figure 6.
Figure 6. Topology of three-stranded  -sheet
formed between the epitope peptide and CDR H3. (A) in Fab 9E10,
(B) Fab 447-52D, shown as ribbon representations. Orientations
and color codings are the same as in Figure 5(B).
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2008,
73,
552-565)
copyright 2008.
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