1. Thiol-based switching mechanisms of stress-sensing chaperones
- Author
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Ursula Jakob, Blanche Schwappach, and Kathrin Ulrich
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,High affinity binding ,Clinical Biochemistry ,Protein aggregation ,medicine.disease_cause ,Biochemistry ,Cell biology ,Oxidative Stress ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Foldase ,Stress sensing ,Thiol ,Unfolded protein response ,medicine ,Sulfhydryl Compounds ,Stress conditions ,Molecular Biology ,030217 neurology & neurosurgery ,Oxidative stress ,Molecular Chaperones - Abstract
Thiol-based redox switches evolved as efficient post-translational regulatory mechanisms that enable individual proteins to rapidly respond to sudden environmental changes. While some protein functions need to be switched off to save resources and avoid potentially error-prone processes, protective functions become essential and need to be switched on. In this review, we focus on thiol-based activation mechanisms of stress-sensing chaperones. Upon stress exposure, these chaperones convert into high affinity binding platforms for unfolding proteins and protect cells against the accumulation of potentially toxic protein aggregates. Their chaperone activity is independent of ATP, a feature that becomes especially important under oxidative stress conditions, where cellular ATP levels drop and canonical ATP-dependent chaperones no longer operate. Vice versa, reductive inactivation and substrate release require the restoration of ATP levels, which ensures refolding of client proteins by ATP-dependent foldases. We will give an overview over the different strategies that cells evolved to rapidly increase the pool of ATP-independent chaperones upon oxidative stress and provide mechanistic insights into how stress conditions are used to convert abundant cellular proteins into ATP-independent holding chaperones.
- Published
- 2020