The UzcRS two‐component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators. Issue 3 (3rd February 2019)

• Record Type: Journal Article
• Authors: Park, Dan M.; Overton, K. Wesley; Jiao, Yongqin
• Is Part Of: Molecular microbiology. Volume 111:Issue 3(2019)
• Page Start: 678
• Page End: 699
• Publication Date: 2019-02-03
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14180
• Languages: English
• ISSNs: 0950-382X

Abstract

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. Abstract : Regulatory proteins beyond the histidine kinase and response regulator play important roles in the signal perception and transduction process of two‐component systems (TCS). Here, we find that the U/Zn/Cu‐responsive TCS UzcRS in C. crescentus integrates regulatory input from four previously uncharacterized protein regulators. This regulatory interplay ensures low UzcRS activity in the absence of inducer, modulates the sensitivity of UzcRS to its inducers, and connects UzcRS with otherwise independent regulatory pathways.