Work

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

Year: 2022

Type: article

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.

Source: npj Systems Biology and Applications

DOI: 10.1038/s41540-022-00256-3

Authors: Dezerae Cox, Angelique R. Ormsby, Gavin E. Reid, Danny M. Hatters

Institutions: The University of Melbourne, University of Cambridge

Language: English

Topic: Advanced Proteomics Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,090