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Title: Cell fate regulation governed by a repurposed bacterial histidine kinase

One of the simplest organisms to divide asymmetrically is the bacterium Caulobacter crescentus. The DivL pseudo-histidine kinase, positioned at one cell pole, regulates cell-fate by controlling the activation of the global transcription factor CtrA via an interaction with the response regulator (RR) DivK. DivL uniquely contains a tyrosine at the histidine phosphorylation site, and can achieve these regulatory functions in vivo without kinase activity. Determination of the DivL crystal structure and biochemical analysis of wild-type and site-specific DivL mutants revealed that the DivL PAS domains regulate binding specificity for DivK~P over DivK, which is modulated by an allosteric intramolecular interaction between adjacent domains. We discovered that DivL's catalytic domains have been repurposed as a phosphospecific RR input sensor, thereby reversing the flow of information observed in conventional histidine kinase (HK)-RR systems and coupling a complex network of signaling proteins for cell-fate regulation.
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [3]
  1. Stanford Univ. School of Medicine, Stanford, CA (United States)
  2. SLAC National Accelerator Laboratory, Menlo Park, CA (United States)
  3. Rutgers Univ., New Brunswick, NJ (United States)
Publication Date:
Grant/Contract Number:
AC03-76SF00515
Type:
Accepted Manuscript
Journal Name:
PLoS biology (Online)
Additional Journal Information:
Journal Name: PLoS biology (Online); Journal Volume: 12; Journal Issue: 10; Journal ID: ISSN 1545-7885
Publisher:
Public Library of Science
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; phosphorylation; xylose; binding analysis; cell cycle and cell division; point mutation; crystal structure; caulobacter; histidine
OSTI Identifier:
1213908

Childers, W. Seth, Xu, Qingping, Mann, Thomas H., Mathews, Irimpan I., Blair, Jimmy A., Deacon, Ashley M., Shapiro, Lucy, and Stock, Ann M.. Cell fate regulation governed by a repurposed bacterial histidine kinase. United States: N. p., Web. doi:10.1371/journal.pbio.1001979.
Childers, W. Seth, Xu, Qingping, Mann, Thomas H., Mathews, Irimpan I., Blair, Jimmy A., Deacon, Ashley M., Shapiro, Lucy, & Stock, Ann M.. Cell fate regulation governed by a repurposed bacterial histidine kinase. United States. doi:10.1371/journal.pbio.1001979.
Childers, W. Seth, Xu, Qingping, Mann, Thomas H., Mathews, Irimpan I., Blair, Jimmy A., Deacon, Ashley M., Shapiro, Lucy, and Stock, Ann M.. 2014. "Cell fate regulation governed by a repurposed bacterial histidine kinase". United States. doi:10.1371/journal.pbio.1001979. https://www.osti.gov/servlets/purl/1213908.
@article{osti_1213908,
title = {Cell fate regulation governed by a repurposed bacterial histidine kinase},
author = {Childers, W. Seth and Xu, Qingping and Mann, Thomas H. and Mathews, Irimpan I. and Blair, Jimmy A. and Deacon, Ashley M. and Shapiro, Lucy and Stock, Ann M.},
abstractNote = {One of the simplest organisms to divide asymmetrically is the bacterium Caulobacter crescentus. The DivL pseudo-histidine kinase, positioned at one cell pole, regulates cell-fate by controlling the activation of the global transcription factor CtrA via an interaction with the response regulator (RR) DivK. DivL uniquely contains a tyrosine at the histidine phosphorylation site, and can achieve these regulatory functions in vivo without kinase activity. Determination of the DivL crystal structure and biochemical analysis of wild-type and site-specific DivL mutants revealed that the DivL PAS domains regulate binding specificity for DivK~P over DivK, which is modulated by an allosteric intramolecular interaction between adjacent domains. We discovered that DivL's catalytic domains have been repurposed as a phosphospecific RR input sensor, thereby reversing the flow of information observed in conventional histidine kinase (HK)-RR systems and coupling a complex network of signaling proteins for cell-fate regulation.},
doi = {10.1371/journal.pbio.1001979},
journal = {PLoS biology (Online)},
number = 10,
volume = 12,
place = {United States},
year = {2014},
month = {10}
}