The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division. Physical and Life Sciences Directorate
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.
- Research Organization:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); LLNL Laboratory Directed Research and Development (LDRD) Program; National Inst. of Health (NIH) (United States)
- Grant/Contract Number:
- AC52-07NA27344; S10 OD018174
- OSTI ID:
- 1513159
- Alternate ID(s):
- OSTI ID: 1787157
- Report Number(s):
- LLNL-JRNL-743338; 898425
- Journal Information:
- Molecular microbiology, Vol. 111, Issue 3; ISSN 0950-382X
- Publisher:
- WileyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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