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Title: The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators

Abstract

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 here 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.

Authors:
 [1];  [1];  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division. Physical and Life Sciences Directorate
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); LLNL Laboratory Directed Research and Development (LDRD) Program; National Inst. of Health (NIH) (United States)
OSTI Identifier:
1513159
Report Number(s):
LLNL-JRNL-743338
Journal ID: ISSN 0950-382X; 898425
Grant/Contract Number:  
AC52-07NA27344; S10 OD018174
Resource Type:
Accepted Manuscript
Journal Name:
Molecular microbiology
Additional Journal Information:
Journal Volume: 111; Journal Issue: 3; Journal ID: ISSN 0950-382X
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Park, Dan M., Wesley Overton, K., and Jiao, Yongqin. The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators. United States: N. p., 2018. Web. doi:10.1111/mmi.14180.
Park, Dan M., Wesley Overton, K., & Jiao, Yongqin. The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators. United States. doi:10.1111/mmi.14180.
Park, Dan M., Wesley Overton, K., and Jiao, Yongqin. Sat . "The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators". United States. doi:10.1111/mmi.14180.
@article{osti_1513159,
title = {The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators},
author = {Park, Dan M. and Wesley Overton, K. and Jiao, Yongqin},
abstractNote = {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 (PurcA) revealed four previously uncharacterized proteins whose inactivation led to metal-independent induction of PurcA. Using molecular genetics and functional genomics, we find here that these auxiliary regulators control PurcA 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.},
doi = {10.1111/mmi.14180},
journal = {Molecular microbiology},
number = 3,
volume = 111,
place = {United States},
year = {2018},
month = {12}
}

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This content will become publicly available on December 8, 2019
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