title: 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.
abstract: 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.
authors.affiliation: Institut für Biochemie, Charité, Universitätsmedizin Berlin, Monbijoustr. 2, D-10117 Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Krauss
authors.forename: Helga
authors.initials: H
authors.lastname: Wessner
authors.forename: Karin
authors.initials: K
authors.lastname: Welfle
authors.forename: Heinz
authors.initials: H
authors.lastname: Welfle
authors.forename: Christa
authors.initials: C
authors.lastname: Scholz
authors.forename: Martina
authors.initials: M
authors.lastname: Seifert
authors.forename: Kristina
authors.initials: K
authors.lastname: Zubow
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Aÿ
authors.forename: Michael
authors.initials: M
authors.lastname: Hahn
authors.forename: Patrick
authors.initials: P
authors.lastname: Scheerer
authors.forename: Arne
authors.initials: A
authors.lastname: Skerra
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höhne
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry*; D002151:Calorimetry; D002460:Cell Line; D022801:Complementarity Determining Regions / Q000737:chemistry; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology*; D013816:Thermodynamics
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc