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:
https://lup.lub.lu.se/record/3161140
- author
- Olsson, Niclas
LU
; Wallin, Stefan
LU
; James, Peter
LU
; Borrebaeck, Carl
LU
and Wingren, Christer
LU
- organization
- publishing date
- 2012
- 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
- pmid:23034898
- ISSN
- 1469-896X
- DOI
- 10.1002/pro.2173
- language
- English
- LU publication?
- yes
- id
- eeb9cd35-4dca-4dc7-8474-3b922180da88 (old id 3161140)
- date added to LUP
- 2016-04-01 09:48:20
- date last changed
- 2024-01-06 00:16:59
@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}},
keywords = {{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}},
doi = {{10.1002/pro.2173}},
volume = {{21}},
year = {{2012}},
}