Key Points
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Proteolysis in bacteria is important not only for protein homeostasis and quality control (general proteolysis), but also for the control of regulatory processes such as adaptation and cell development (regulatory proteolysis).
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In bacteria, self-compartmentalized ATP-dependent proteases of the AAA+ protein family, such as different Hsp100/Clp protease complexes and AAA+ proteases, are responsible for general and regulatory proteolysis.
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Substrate recognition by these proteases seems to be an interplay between endogenously encoded degrons, additional processes that generate new degrons and adaptor proteins recognizing the substrates.
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Adaptor proteins interact simultaneously with substrates and subdomains of the AAA+ protein domain, thereby targeting the substrates for degradation by the cognate proteases. Adaptor proteins can also be required for the modulation of the activity of certain AAA+ proteins.
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These adaptor proteins may also themselves be regulated (for example, by small anti-adaptor proteins and/or phosphorylation) and have important roles in a range of regulatory processes, such as competence development, heat shock adaptation and sporulation in Bacillus subtilis and the general stress response in Escherichia coli.
Abstract
Members of the AAA+ protein superfamily contribute to many diverse aspects of protein homeostasis in prokaryotic cells. As a fundamental component of numerous proteolytic machines in bacteria, AAA+ proteins play a crucial part not only in general protein quality control but also in the regulation of developmental programmes, through the controlled turnover of key proteins such as transcription factors. To manage these many, varied tasks, Hsp100/Clp and AAA+ proteases use specific adaptor proteins to enhance or expand the substrate recognition abilities of their cognate protease. Here, we review our current knowledge of the modulation of bacterial AAA+ proteases by these cellular arbitrators.
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Acknowledgements
We thank J. Hahn, R. Hengge and G. Becker for critical reading and comments. Work in the laboratory of K.T. is supported by the Deutsche Forschungsgemeinschaft. J.K. is currently supported by a long-term postdoctoral fellowship from the Human Frontier Science Program (LT00045/2008-L). D.A.D. is supported by a QEII Fellowship from the Australian Research Council (DP0450051).
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Glossary
- Chaperone
-
Protein that assists the folding of another protein, either by promoting folding or by stabilizing a partially folded intermediate.
- AAA+
-
A member of a superfamily of proteins that assemble into higher-order structures and that use the energy of ATP hydrolysis to unfold proteins and, in some cases, transfer the unfolded protein into a protease.
- Degron
-
A recognition sequence in a protein that targets it for degradation by a protease.
- Ubiquitin
-
A small protein that is added to eukaryotic proteins. Ubiquitin acts as a recognition signal for the proteasome and causes the degradation of the target protein.
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Kirstein, J., Molière, N., Dougan, D. et al. Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases. Nat Rev Microbiol 7, 589–599 (2009). https://doi.org/10.1038/nrmicro2185
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DOI: https://doi.org/10.1038/nrmicro2185
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