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

Item Type:	Article
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
Creators Name:	Krauss, N. and Wessner, H. and Welfle, K. and Welfle, H. and Scholz, C. and Seifert, M. and Zubow, K. and Ay, J. and Hahn, M. and Scheerer, P. and Skerra, A. and Hoehne, W.
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.
Keywords:	Antibody-Antigen Interaction, Epitope Peptide, myc-Tag, Crystal Structure, Conformation of Complementarity Determining Regions, Calorimetry
Source:	Proteins: Structure, Function, and Bioinformatics
ISSN:	0887-3585
Publisher:	Wiley
Volume:	73
Number:	3
Page Range:	552-565
Date:	15 November 2008
Official Publication:	https://doi.org/10.1002/prot.22080
PubMed:	View item in PubMed

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