Peter James
Professor
Epitope-specificity of recombinant antibodies reveals promiscuous peptide-binding properties.
Author
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 - Has been reorganised
- 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