Structure of an Anti-Cholera Toxin Antibody Fab in Complex With an Epitope-Derived D-peptide: A Case of Polyspecific Recognition

J Mol Recognit. Jul-Aug 2007;20(4):263-74. doi: 10.1002/jmr.838.

Abstract

The structure of a complex of the anti-cholera toxin antibody TE33 Fab (fragment antibody) with the D-peptide vpGsqhyds was solved to 1.78 A resolution. The D-peptide was derived from the linear L-peptide epitope VPGSQHIDS by a stepwise transformation. Despite the very similar amino acid sequence-the only difference is a tyrosine residue in position 7-there are marked differences in the individual positions with respect to their contribution to the peptide overall affinity as ascertained by a complete substitutional analysis. This is reflected by the X-ray structure of the TE33 Fab/D-peptide complex where there is an inverted orientation of the D-peptide as compared with the known structure of a corresponding complex containing the epitope L-peptide, with the side chains establishing different contacts within the binding site of TE33. The D- and L-peptide affinities are comparable and the surface areas buried by complex formation are almost the same. Thus the antibody TE33 provides a typical example for polyspecific binding behavior of IgG family antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Antigen-Antibody Complex / analysis
  • Antigen-Antibody Complex / chemistry*
  • Binding Sites, Antibody
  • Cholera Toxin / immunology*
  • Cross Reactions
  • Crystallography, X-Ray
  • Epitopes / chemistry
  • Epitopes / metabolism*
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Interaction Mapping
  • Protein Structure, Tertiary

Substances

  • Antigen-Antibody Complex
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Peptides
  • Cholera Toxin