Mass spectrometry reveals the direct action of a chemical chaperone
Despite their fundamental biological importance and therapeutic potential, the interactions between chemical chaperones and proteins remain difficult to capture due to their transient and nonspecific nature. Using a simple mass spectrometric assay, we are able to follow the interactions between prot...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
American Chemical Society
2018
|
_version_ | 1826286369579728896 |
---|---|
author | Gault, J Lianoudaki, D Kaldmäe, M Kronqvist, N Rising, A Johansson, J Lohkamp, B Laín, S Allison, T Lane, D Marklund, E Landreh, M |
author_facet | Gault, J Lianoudaki, D Kaldmäe, M Kronqvist, N Rising, A Johansson, J Lohkamp, B Laín, S Allison, T Lane, D Marklund, E Landreh, M |
author_sort | Gault, J |
collection | OXFORD |
description | Despite their fundamental biological importance and therapeutic potential, the interactions between chemical chaperones and proteins remain difficult to capture due to their transient and nonspecific nature. Using a simple mass spectrometric assay, we are able to follow the interactions between proteins and the chemical chaperone trimethylamine-N-oxide (TMAO). In this manner, we directly observe that the counteraction of TMAO and the denaturant urea is driven by the exclusion of TMAO from the protein surface, whereas the surfactant lauryl dimethylamine-N-oxide cannot be displaced. Our results clearly demonstrate a direct chaperoning mechanism for TMAO, corroborating extensive computational studies, and pave the way for the use of nondenaturing mass spectrometry and related techniques to study chemical chaperones in molecular detail. |
first_indexed | 2024-03-07T01:42:43Z |
format | Journal article |
id | oxford-uuid:976886ed-7f30-4d41-baf4-d7af8d724d42 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T01:42:43Z |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | dspace |
spelling | oxford-uuid:976886ed-7f30-4d41-baf4-d7af8d724d422022-03-26T23:59:24ZMass spectrometry reveals the direct action of a chemical chaperoneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:976886ed-7f30-4d41-baf4-d7af8d724d42EnglishSymplectic Elements at OxfordAmerican Chemical Society2018Gault, JLianoudaki, DKaldmäe, MKronqvist, NRising, AJohansson, JLohkamp, BLaín, SAllison, TLane, DMarklund, ELandreh, MDespite their fundamental biological importance and therapeutic potential, the interactions between chemical chaperones and proteins remain difficult to capture due to their transient and nonspecific nature. Using a simple mass spectrometric assay, we are able to follow the interactions between proteins and the chemical chaperone trimethylamine-N-oxide (TMAO). In this manner, we directly observe that the counteraction of TMAO and the denaturant urea is driven by the exclusion of TMAO from the protein surface, whereas the surfactant lauryl dimethylamine-N-oxide cannot be displaced. Our results clearly demonstrate a direct chaperoning mechanism for TMAO, corroborating extensive computational studies, and pave the way for the use of nondenaturing mass spectrometry and related techniques to study chemical chaperones in molecular detail. |
spellingShingle | Gault, J Lianoudaki, D Kaldmäe, M Kronqvist, N Rising, A Johansson, J Lohkamp, B Laín, S Allison, T Lane, D Marklund, E Landreh, M Mass spectrometry reveals the direct action of a chemical chaperone |
title | Mass spectrometry reveals the direct action of a chemical chaperone |
title_full | Mass spectrometry reveals the direct action of a chemical chaperone |
title_fullStr | Mass spectrometry reveals the direct action of a chemical chaperone |
title_full_unstemmed | Mass spectrometry reveals the direct action of a chemical chaperone |
title_short | Mass spectrometry reveals the direct action of a chemical chaperone |
title_sort | mass spectrometry reveals the direct action of a chemical chaperone |
work_keys_str_mv | AT gaultj massspectrometryrevealsthedirectactionofachemicalchaperone AT lianoudakid massspectrometryrevealsthedirectactionofachemicalchaperone AT kaldmaem massspectrometryrevealsthedirectactionofachemicalchaperone AT kronqvistn massspectrometryrevealsthedirectactionofachemicalchaperone AT risinga massspectrometryrevealsthedirectactionofachemicalchaperone AT johanssonj massspectrometryrevealsthedirectactionofachemicalchaperone AT lohkampb massspectrometryrevealsthedirectactionofachemicalchaperone AT lains massspectrometryrevealsthedirectactionofachemicalchaperone AT allisont massspectrometryrevealsthedirectactionofachemicalchaperone AT laned massspectrometryrevealsthedirectactionofachemicalchaperone AT marklunde massspectrometryrevealsthedirectactionofachemicalchaperone AT landrehm massspectrometryrevealsthedirectactionofachemicalchaperone |