Cargando…

Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction

Modulating protein ion charge is a useful tool for the study of protein folding and interactions by electrospray ionization mass spectrometry. Here, we investigate activation-dependent charge reduction of protein ions with the chemical chaperone trimethylamine-N-oxide (TMAO). Based on experiments ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Kaldmäe, Margit, Österlund, Nicklas, Lianoudaki, Danai, Sahin, Cagla, Bergman, Peter, Nyman, Tomas, Kronqvist, Nina, Ilag, Leopold L., Allison, Timothy M., Marklund, Erik G., Landreh, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669196/
https://www.ncbi.nlm.nih.gov/pubmed/31286443
http://dx.doi.org/10.1007/s13361-019-02177-8
_version_ 1783440329848913920
author Kaldmäe, Margit
Österlund, Nicklas
Lianoudaki, Danai
Sahin, Cagla
Bergman, Peter
Nyman, Tomas
Kronqvist, Nina
Ilag, Leopold L.
Allison, Timothy M.
Marklund, Erik G.
Landreh, Michael
author_facet Kaldmäe, Margit
Österlund, Nicklas
Lianoudaki, Danai
Sahin, Cagla
Bergman, Peter
Nyman, Tomas
Kronqvist, Nina
Ilag, Leopold L.
Allison, Timothy M.
Marklund, Erik G.
Landreh, Michael
author_sort Kaldmäe, Margit
collection PubMed
description Modulating protein ion charge is a useful tool for the study of protein folding and interactions by electrospray ionization mass spectrometry. Here, we investigate activation-dependent charge reduction of protein ions with the chemical chaperone trimethylamine-N-oxide (TMAO). Based on experiments carried out on proteins ranging from 4.5 to 35 kDa, we find that when combined with collisional activation, TMAO removes approximately 60% of the charges acquired under native conditions. Ion mobility measurements furthermore show that TMAO-mediated charge reduction produces the same end charge state and arrival time distributions for native-like and denatured protein ions. Our results suggest that gas-phase collisions between the protein ions and TMAO result in proton transfer, in line with previous findings for dimethyl- and trimethylamine. By adjusting the energy of the collisions experienced by the ions, it is possible to control the degree of charge reduction, making TMAO a highly dynamic charge reducer that opens new avenues for manipulating protein charge states in ESI-MS and for investigating the relationship between protein charge and conformation. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13361-019-02177-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6669196
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-66691962019-08-14 Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction Kaldmäe, Margit Österlund, Nicklas Lianoudaki, Danai Sahin, Cagla Bergman, Peter Nyman, Tomas Kronqvist, Nina Ilag, Leopold L. Allison, Timothy M. Marklund, Erik G. Landreh, Michael J Am Soc Mass Spectrom Focus: Emerging Investigators: Short Communication Modulating protein ion charge is a useful tool for the study of protein folding and interactions by electrospray ionization mass spectrometry. Here, we investigate activation-dependent charge reduction of protein ions with the chemical chaperone trimethylamine-N-oxide (TMAO). Based on experiments carried out on proteins ranging from 4.5 to 35 kDa, we find that when combined with collisional activation, TMAO removes approximately 60% of the charges acquired under native conditions. Ion mobility measurements furthermore show that TMAO-mediated charge reduction produces the same end charge state and arrival time distributions for native-like and denatured protein ions. Our results suggest that gas-phase collisions between the protein ions and TMAO result in proton transfer, in line with previous findings for dimethyl- and trimethylamine. By adjusting the energy of the collisions experienced by the ions, it is possible to control the degree of charge reduction, making TMAO a highly dynamic charge reducer that opens new avenues for manipulating protein charge states in ESI-MS and for investigating the relationship between protein charge and conformation. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13361-019-02177-8) contains supplementary material, which is available to authorized users. Springer US 2019-07-08 2019 /pmc/articles/PMC6669196/ /pubmed/31286443 http://dx.doi.org/10.1007/s13361-019-02177-8 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Focus: Emerging Investigators: Short Communication
Kaldmäe, Margit
Österlund, Nicklas
Lianoudaki, Danai
Sahin, Cagla
Bergman, Peter
Nyman, Tomas
Kronqvist, Nina
Ilag, Leopold L.
Allison, Timothy M.
Marklund, Erik G.
Landreh, Michael
Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title_full Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title_fullStr Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title_full_unstemmed Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title_short Gas-Phase Collisions with Trimethylamine-N-Oxide Enable Activation-Controlled Protein Ion Charge Reduction
title_sort gas-phase collisions with trimethylamine-n-oxide enable activation-controlled protein ion charge reduction
topic Focus: Emerging Investigators: Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669196/
https://www.ncbi.nlm.nih.gov/pubmed/31286443
http://dx.doi.org/10.1007/s13361-019-02177-8
work_keys_str_mv AT kaldmaemargit gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT osterlundnicklas gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT lianoudakidanai gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT sahincagla gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT bergmanpeter gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT nymantomas gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT kronqvistnina gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT ilagleopoldl gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT allisontimothym gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT marklunderikg gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction
AT landrehmichael gasphasecollisionswithtrimethylaminenoxideenableactivationcontrolledproteinionchargereduction