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...

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Main Authors: Gault, J, Lianoudaki, D, Kaldmäe, M, Kronqvist, N, Rising, A, Johansson, J, Lohkamp, B, Laín, S, Allison, T, Lane, D, Marklund, E, Landreh, M
Format: Journal article
Language:English
Published: American Chemical Society 2018
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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.
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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
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