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.
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.
Krauss
Norbert
N
Institut für Biochemie, Charité, Universitätsmedizin Berlin, Monbijoustr. 2, D-10117 Berlin, Germany.
Wessner
Helga
H
Welfle
Karin
K
Welfle
Heinz
H
Scholz
Christa
C
Seifert
Martina
M
Zubow
Kristina
K
Aÿ
Jacqueline
J
Hahn
Michael
M
Scheerer
Patrick
P
Skerra
Arne
A
Höhne
Wolfgang
W
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
D000906:Antibodies; D022801:Complementarity Determining Regions; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc