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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
Author(s) -
Krauß Norbert,
Wessner Helga,
Welfle Karin,
Welfle Heinz,
Scholz Christa,
Seifert Martina,
Zubow Kristina,
Aÿ Jacqueline,
Hahn Michael,
Scheerer Patrick,
Skerra Arne,
Höhne Wolfgang
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22080
Subject(s) - antiparallel (mathematics) , peptide , chemistry , epitope , stereochemistry , dimer , peptide sequence , immunoglobulin fab fragments , crystallography , antibody , complementarity determining region , biochemistry , biology , genetics , physics , organic chemistry , quantum mechanics , magnetic field , gene
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 β‐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. Proteins 2008. © 2008 Wiley‐Liss, Inc.