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

Olsson, Niclas LU ; Wallin, Stefan LU ; James, Peter LU ; Borrebaeck, Carl LU and Wingren, Christer LU (2012) In Protein Science 21(12). p.1897-1910
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibody specificity, anti-peptide antibody, peptide binding, immunoaffinity peptide capture, mass spectrometry
in
Protein Science
volume
21
issue
12
pages
1897 - 1910
publisher
The Protein Society
external identifiers
  • pmid:23034898
  • wos:000311616200010
  • scopus:84870309091
ISSN
1469-896X
DOI
10.1002/pro.2173
project
CREATE Health
language
English
LU publication?
yes
id
eeb9cd35-4dca-4dc7-8474-3b922180da88 (old id 3161140)
date added to LUP
2012-11-13 13:24:34
date last changed
2017-09-03 03:00:18
@article{eeb9cd35-4dca-4dc7-8474-3b922180da88,
  abstract     = {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.},
  author       = {Olsson, Niclas and Wallin, Stefan and James, Peter and Borrebaeck, Carl and Wingren, Christer},
  issn         = {1469-896X},
  keyword      = {antibody specificity,anti-peptide antibody,peptide binding,immunoaffinity peptide capture,mass spectrometry},
  language     = {eng},
  number       = {12},
  pages        = {1897--1910},
  publisher    = {The Protein Society},
  series       = {Protein Science},
  title        = {Epitope-specificity of recombinant antibodies reveals promiscuous peptide-binding properties.},
  url          = {http://dx.doi.org/10.1002/pro.2173},
  volume       = {21},
  year         = {2012},
}