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Carl Borrebaeck

Carl Borrebaeck

Professor

Carl Borrebaeck

Epitope-specificity of recombinant antibodies reveals promiscuous peptide-binding properties.

Author

  • Niclas Olsson
  • Stefan Wallin
  • Peter James
  • Carl Borrebaeck
  • Christer Wingren

Summary, in English

Protein-peptide interactions are a common occurrence and essential for numerous cellular processes, and frequently explored in broad applications within biology, medicine, and proteomics. Therefore, understanding the molecular mechanism(s) of protein-peptide recognition, specificity, and binding interactions will be essential. In this study, we report the first detailed analysis of antibody-peptide interaction characteristics, by combining large-scale experimental peptide binding data with the structural analysis of eight human recombinant antibodies and numerous peptides, targeting tryptic mammalian and eukaryote proteomes. The results consistently revealed that promiscuous peptide-binding interactions, that is, both specific and degenerate binding, were exhibited by all antibodies, and the discovery was corroborated by orthogonal data, indicating that this might be a general phenomenon for low-affinity antibody-peptide interactions. The molecular mechanism for the degenerate peptide-binding specificity appeared to be executed through the use of 2-3 semi-conserved anchor residues in the C-terminal part of the peptides, in analogue to the mechanism utilized by the major histocompatibility complex-peptide complexes. In the long-term, this knowledge will be instrumental for advancing our fundamental understanding of protein-peptide interactions, as well as for designing, generating, and applying peptide specific antibodies, or peptide-binding proteins in general, in various biotechnical and medical applications.

Department/s

  • Department of Immunotechnology
  • Computational Biology and Biological Physics - Undergoing reorganization
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2012

Language

English

Pages

1897-1910

Publication/Series

Protein Science

Volume

21

Issue

12

Document type

Journal article

Publisher

The Protein Society

Topic

  • Immunology in the medical area

Keywords

  • antibody specificity
  • anti-peptide antibody
  • peptide binding
  • immunoaffinity peptide capture
  • mass spectrometry

Status

Published

ISBN/ISSN/Other

  • ISSN: 1469-896X