Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli

Autor: Dezerae Cox, Angelique R. Ormsby, Gavin E. Reid, Danny M. Hatters
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: npj Systems Biology and Applications, Vol 8, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2056-7189
DOI: 10.1038/s41540-022-00256-3
Popis: Abstract The correct spatio-temporal organization of the proteome is essential for cellular homeostasis. However, a detailed mechanistic understanding of this organization and how it is altered in response to external stimuli in the intact cellular environment is as-yet unrealized. ‘Protein painting methods provide a means to address this gap in knowledge by monitoring the conformational status of proteins within cells at the proteome-wide scale. Here, we demonstrate the ability of a protein painting method employing tetraphenylethene maleimide (TPE-MI) to reveal proteome network remodeling in whole cells in response to a cohort of commonly used pharmacological stimuli of varying specificity. We report specific, albeit heterogeneous, responses to individual stimuli that coalesce on a conserved set of core cellular machineries. This work expands our understanding of proteome conformational remodeling in response to cellular stimuli, and provides a blueprint for assessing how these conformational changes may contribute to disorders characterized by proteostasis imbalance.
Databáze: Directory of Open Access Journals
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