4.5 Article

Structural determinants of regulated proteolysis in pathogenic bacteria by ClpP and the proteasome

Journal

CURRENT OPINION IN STRUCTURAL BIOLOGY
Volume 67, Issue -, Pages 120-126

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2020.09.012

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Funding

  1. NIH [AI144851, AI088075]

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Bacteria use proteolytic machines for protein quality control and response to environmental conditions, with ClpP proteases and bacterial proteasomes being common mechanisms, where activators play a key role. Understanding these mechanisms can lead to new approaches in designing targeted therapeutics.
Bacteria use gated proteolytic machines for routine protein quality control and regulated responses to environmental conditions. This review discusses recent advances in understanding the structure and regulation of ClpP proteases, nanomachines widely distributed across bacteria, and the bacterial proteasome, a protease found in relatively few species. For both machines, activators confer substrate specificity. We highlight new data from organisms encoding two ClpP isoforms and the central role of activators as platforms for integrating regulatory signals. Because proteolytic systems contribute to survival and virulence of many bacterial pathogens, understanding their forms and functions enables new approaches to design targeted therapeutics.

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