A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria

ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	C. Lori, A. Kaczmarczyk, I. de Jong, U. Jenal
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Caulobacter alphaproteobacteria bow-tie general stress response phosphorylation regulation of gene expression Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8f902c4c0a0d49928b4ef4d8ac8525df
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8f902c4c0a0d49928b4ef4d8ac8525df
record_format	dspace
spelling	oai:doaj.org-article:8f902c4c0a0d49928b4ef4d8ac8525df2021-11-15T16:00:25ZA Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria10.1128/mBio.00809-182150-7511https://doaj.org/article/8f902c4c0a0d49928b4ef4d8ac8525df2018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00809-18https://doaj.org/toc/2150-7511ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria. IMPORTANCE Two-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross talk, TCSs are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alphaproteobacterial general stress response. Here, we show that in the model organism Caulobacter crescentus an atypical FATGUY-type single-domain response regulator, MrrA, is highly promiscuous in accepting and transferring phosphoryl groups from and to multiple up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alphaproteobacteria as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors.C. LoriA. KaczmarczykI. de JongU. JenalAmerican Society for MicrobiologyarticleCaulobacteralphaproteobacteriabow-tiegeneral stress responsephosphorylationregulation of gene expressionMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caulobacter alphaproteobacteria bow-tie general stress response phosphorylation regulation of gene expression Microbiology QR1-502
spellingShingle	Caulobacter alphaproteobacteria bow-tie general stress response phosphorylation regulation of gene expression Microbiology QR1-502 C. Lori A. Kaczmarczyk I. de Jong U. Jenal A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
description	ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria. IMPORTANCE Two-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross talk, TCSs are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alphaproteobacterial general stress response. Here, we show that in the model organism Caulobacter crescentus an atypical FATGUY-type single-domain response regulator, MrrA, is highly promiscuous in accepting and transferring phosphoryl groups from and to multiple up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alphaproteobacteria as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors.
format	article
author	C. Lori A. Kaczmarczyk I. de Jong U. Jenal
author_facet	C. Lori A. Kaczmarczyk I. de Jong U. Jenal
author_sort	C. Lori
title	A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
title_short	A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
title_full	A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
title_fullStr	A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
title_full_unstemmed	A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria
title_sort	single-domain response regulator functions as an integrating hub to coordinate general stress response and development in alphaproteobacteria
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/8f902c4c0a0d49928b4ef4d8ac8525df
work_keys_str_mv	AT clori asingledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT akaczmarczyk asingledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT idejong asingledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT ujenal asingledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT clori singledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT akaczmarczyk singledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT idejong singledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria AT ujenal singledomainresponseregulatorfunctionsasanintegratinghubtocoordinategeneralstressresponseanddevelopmentinalphaproteobacteria
_version_	1718426981716983808

A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria

Ejemplares similares