All bacteria possess ATP-dependent proteases that harness chemical energy to destroy cytosolic proteins. These proteolytic machines frequently regulate aspects of virulence and pathogenesis, and have emerged as promising targets for novel antibacterial drugs. ATP-dependent proteases are generally capable of selectively recognizing bona fide substrates from the complexity of the cytosolic proteome. Some protein substrates are recognized directly, via short unstructured targeting sequences termed degrons. A handful of degrons have been identified to date, but the overarching rules that govern substrate recognition by individual proteases remain poorly defined. Using a novel cell-based selection platform that couples cell survival to degron recognition in E. coli, we are able to systematically identify thousands of functional C-terminal degron sequences. Our results expand our understanding of the proteolytic landscape in bacteria, and highlight the peculiar ability of the ClpXP protease to recognize short degrons.

Systamically mapping the landscape of C-terminal proteolytic degrons in E. coli

ACS Spring Meeting 2021

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