Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>

ABSTRACT The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS)...

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Autores principales:	E. Lesne, E.-M. Krammer, E. Dupre, C. Locht, M. F. Lensink, R. Antoine, F. Jacob-Dubuisson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4ca4fb9354c34c05a978ae46123c9f96
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spelling	oai:doaj.org-article:4ca4fb9354c34c05a978ae46123c9f962021-11-15T15:41:41ZBalance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>10.1128/mBio.02089-152150-7511https://doaj.org/article/4ca4fb9354c34c05a978ae46123c9f962016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02089-15https://doaj.org/toc/2150-7511ABSTRACT The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases. IMPORTANCE The two-component system BvgAS of the whooping cough agent Bordetella pertussis regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase, B. pertussis is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in Bordetella, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.E. LesneE.-M. KrammerE. DupreC. LochtM. F. LensinkR. AntoineF. Jacob-DubuissonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 E. Lesne E.-M. Krammer E. Dupre C. Locht M. F. Lensink R. Antoine F. Jacob-Dubuisson Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
description	ABSTRACT The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases. IMPORTANCE The two-component system BvgAS of the whooping cough agent Bordetella pertussis regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase, B. pertussis is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in Bordetella, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.
format	article
author	E. Lesne E.-M. Krammer E. Dupre C. Locht M. F. Lensink R. Antoine F. Jacob-Dubuisson
author_facet	E. Lesne E.-M. Krammer E. Dupre C. Locht M. F. Lensink R. Antoine F. Jacob-Dubuisson
author_sort	E. Lesne
title	Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
title_short	Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
title_full	Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
title_fullStr	Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
title_full_unstemmed	Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>
title_sort	balance between coiled-coil stability and dynamics regulates activity of bvgs sensor kinase in <italic toggle="yes">bordetella</italic>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/4ca4fb9354c34c05a978ae46123c9f96
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Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in <italic toggle="yes">Bordetella</italic>

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