Mycobacterium tuberculosis Rv0991c Is a Redox-Regulated Molecular Chaperone
Autor: | William N. Beavers, Avantika Dhabaria, Ursula Jakob, L. Aravind, Kathrin Ulrich, Samuel H. Becker, Lakshminarayan M. Iyer, Eric P. Skaar, Beatrix Ueberheide, K. Heran Darwin |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Protein Folding
Molecular Biology and Physiology Tuberculosis Virulence Microbiology Hsp70 Mycobacterium Mycobacterium tuberculosis 03 medical and health sciences Mice 0302 clinical medicine Bacterial Proteins Virology medicine Animals Humans chaperone Pathogen Heat-Shock Proteins 030304 developmental biology 0303 health sciences proteostasis biology Protein Stability Chemistry Escherichia coli Proteins biology.organism_classification medicine.disease QR1-502 Cell biology Mice Inbred C57BL Oxidative Stress Proteostasis Proteotoxicity tuberculosis Chaperone (protein) Hsp33 biology.protein HSP60 Female protein Oxidation-Reduction 030217 neurology & neurosurgery Molecular Chaperones Research Article |
Zdroj: | mBio, Vol 11, Iss 4 (2020) mBio |
ISSN: | 2150-7511 |
DOI: | 10.1128/mBio.01545-20 |
Popis: | M. tuberculosis infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of M. tuberculosis biology. As in all cells, protein quality control is essential for the viability of M. tuberculosis, which likely faces proteotoxic stress within a host. Here, we identify an M. tuberculosis protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential M. tuberculosis Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability. The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. tuberculosis protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacterial lineages and appears to function analogously to the well-characterized Escherichia coli redox-regulated chaperone Hsp33, despite a dissimilar protein sequence. Rv0991c is transcriptionally coregulated with hsp60 and hsp70 chaperone genes in M. tuberculosis, suggesting that Rv0991c functions with these chaperones in maintaining protein quality control. Supporting this hypothesis, we found that, like oxidized Hsp33, oxidized Rv0991c prevents the aggregation of a model unfolded protein in vitro and promotes its refolding by the M. tuberculosis Hsp70 chaperone system. Furthermore, Rv0991c interacts with DnaK and can associate with many other M. tuberculosis proteins. We therefore propose that Rv0991c, which we named “Ruc” (redox-regulated protein with unstructured C terminus), represents a founding member of a new chaperone family that protects M. tuberculosis and other species from proteotoxicity during oxidative stress. |
Databáze: | OpenAIRE |
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