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The UzcRS two‐component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators
Author(s) -
Park Dan M.,
Overton K. Wesley,
Jiao Yongqin
Publication year - 2019
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14180
Subject(s) - caulobacter crescentus , biology , response regulator , periplasmic space , microbiology and biotechnology , two component regulatory system , signal transduction , transcription factor , transcriptional regulation , regulation of gene expression , mutant , transcription (linguistics) , gene , genetics , biochemistry , bacterial protein , linguistics , philosophy , escherichia coli
Summary The UzcRS two‐component system in Caulobacter crescentus mediates widespread transcriptional activation in response to the metals U, Zn and Cu. Unexpectedly, a screen for mutations that affected the activity of the UzcR‐regulated urcA promoter (P urcA ) revealed four previously uncharacterized proteins whose inactivation led to metal‐independent induction of P urcA . Using molecular genetics and functional genomics, we find that these auxiliary regulators control P urcA expression by modulating the activity of UzcRS through distinct mechanisms. An ABC transporter with a periplasmic metallo‐aminopeptidase domain forms a sensory complex with UzcRS, antagonizing metal dependent stimulation by virtue of its ATPase and peptidase domains. Two MarR‐like transcription factors synergistically regulate UzcRS activity by repressing the expression of the membrane proteins UzcY and UzcZ, which stimulate UzcRS activity and enhance its sensitivity to a more environmentally relevant U/Zn/Cu concentration range. Additionally, the membrane protein UzcX, whose expression is positively regulated by UzcR, provides a mechanism of feedback inhibition within the UzcRS circuit. Collectively, these data suggest that UzcRS functions as the core‐signaling unit within a multicomponent signal transduction pathway that includes a diverse set of auxiliary regulators, providing further insight into the complexity of signaling networks.