PT  - JOURNAL ARTICLE
AU  - Dezerae Cox
AU  - Angelique R. Ormsby
AU  - Gavin E. Reid
AU  - Danny M. Hatters
TI  - Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli
AID  - 10.1101/2022.05.14.491969
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.14.491969
4099  - http://biorxiv.org/content/early/2022/05/29/2022.05.14.491969.short
4100  - http://biorxiv.org/content/early/2022/05/29/2022.05.14.491969.full
AB  - Accurate 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. To address this need, ‘protein painting’ methods have emerged as a way to gain insight into the conformational status of proteins within cells at the proteome-wide scale. For example, tetraphenylethene maleimide (TPE-MI) has previously been used to quantify the engagement of quality control machinery with client proteins in cell lysates. Here, we showcase the ability of TPE-MI to additionally 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.Competing Interest StatementThe authors have declared no competing interest.