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Title: A Click‐Chemistry‐Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry

Abstract

Mass spectrometry is the method of choice for the characterisation of proteomes. Most proteins operate in protein complexes, in which their close association modulates their function. However, with standard MS analysis, information on protein–protein interactions is lost and no structural information is retained. To gain structural and interactome data, new crosslinking reagents are needed that freeze inter- and intramolecular interactions. Herein, the development of a new reagent, which has several features that enable highly sensitive crosslinking MS, is reported. The reagent enables enrichment of crosslinked peptides from the majority of background peptides to facilitate efficient detection of low-abundant crosslinked peptides. Due to the special cleavable properties, the reagent can be used for MS2 and potentially for MS3 experiments. Thus, the new crosslinking reagent, in combination with high-end MS, should enable sensitive analysis of interactomes, which will help researchers to obtain important insights into cellular states in health and diseases.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [2]; ORCiD logo [3]; ORCiD logo [2]
  1. Department of ChemistryLudwig-Maximilians-Universität München Butenandtstrasse 5–13 81377 Munich Germany, Department of Molecular Biology and theLewis-Sigler Institute for Integrative GenomicsPrinceton University Washington Road Princeton NJ 08544 USA
  2. Department of ChemistryLudwig-Maximilians-Universität München Butenandtstrasse 5–13 81377 Munich Germany
  3. Department of Molecular Biology and theLewis-Sigler Institute for Integrative GenomicsPrinceton University Washington Road Princeton NJ 08544 USA
Publication Date:
Research Org.:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1592509
Alternate Identifier(s):
OSTI ID: 1592510; OSTI ID: 1623501
Grant/Contract Number:  
SC0018260
Resource Type:
Published Article
Journal Name:
ChemBioChem: a European journal of chemical biology
Additional Journal Information:
Journal Name: ChemBioChem: a European journal of chemical biology Journal Volume: 21 Journal Issue: 1-2; Journal ID: ISSN 1439-4227
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
France
Language:
English
Subject:
Biochemistry & Molecular Biology; Pharmacology & Pharmacy

Citation Formats

Stadlmeier, Michael, Runtsch, Leander Simon, Streshnev, Filipp, Wühr, Martin, and Carell, Thomas. A Click‐Chemistry‐Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry. France: N. p., 2019. Web. doi:10.1002/cbic.201900611.
Stadlmeier, Michael, Runtsch, Leander Simon, Streshnev, Filipp, Wühr, Martin, & Carell, Thomas. A Click‐Chemistry‐Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry. France. doi:https://doi.org/10.1002/cbic.201900611
Stadlmeier, Michael, Runtsch, Leander Simon, Streshnev, Filipp, Wühr, Martin, and Carell, Thomas. Thu . "A Click‐Chemistry‐Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry". France. doi:https://doi.org/10.1002/cbic.201900611.
@article{osti_1592509,
title = {A Click‐Chemistry‐Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry},
author = {Stadlmeier, Michael and Runtsch, Leander Simon and Streshnev, Filipp and Wühr, Martin and Carell, Thomas},
abstractNote = {Mass spectrometry is the method of choice for the characterisation of proteomes. Most proteins operate in protein complexes, in which their close association modulates their function. However, with standard MS analysis, information on protein–protein interactions is lost and no structural information is retained. To gain structural and interactome data, new crosslinking reagents are needed that freeze inter- and intramolecular interactions. Herein, the development of a new reagent, which has several features that enable highly sensitive crosslinking MS, is reported. The reagent enables enrichment of crosslinked peptides from the majority of background peptides to facilitate efficient detection of low-abundant crosslinked peptides. Due to the special cleavable properties, the reagent can be used for MS2 and potentially for MS3 experiments. Thus, the new crosslinking reagent, in combination with high-end MS, should enable sensitive analysis of interactomes, which will help researchers to obtain important insights into cellular states in health and diseases.},
doi = {10.1002/cbic.201900611},
journal = {ChemBioChem: a European journal of chemical biology},
number = 1-2,
volume = 21,
place = {France},
year = {2019},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: https://doi.org/10.1002/cbic.201900611

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