Mostrar el registro sencillo del ítem
dc.contributor.author
Novoa Aponte, Lorena
dc.contributor.author
Xu, Cheng
dc.contributor.author
Soncini, Fernando Carlos
dc.contributor.author
Argüello, José M.
dc.date.available
2022-11-11T01:11:04Z
dc.date.issued
2020-12
dc.identifier.citation
Novoa Aponte, Lorena; Xu, Cheng; Soncini, Fernando Carlos; Argüello, José M.; The Two-Component System CopRS Maintains Subfemtomolar Levels of Free Copper in the Periplasm of Pseudomonas aeruginosa Using a Phosphatase-Based Mechanism; American Society for Microbiology; mSphere; 5; 6; 12-2020; 1-15
dc.identifier.uri
http://hdl.handle.net/11336/177383
dc.description.abstract
Two-component systems control periplasmic Cu1 homeostasis in Gramnegative bacteria. In characterized systems such as Escherichia coli CusRS, upon Cu1 binding to the periplasmic sensing region of CusS, a cytoplasmic phosphotransfer domain of the sensor phosphorylates the response regulator CusR. This drives the expression of efflux transporters, chaperones, and redox enzymes to ameliorate metal toxic effects. Here, we show that the Pseudomonas aeruginosa two-component sensor histidine kinase CopS exhibits a Cu-dependent phosphatase activity that maintains CopR in a nonphosphorylated state when the periplasmic Cu levels are below the activation threshold of CopS. Upon Cux+ binding to the sensor, the phosphatase activity is blocked and the phosphorylated CopR activates transcription of the CopRS regulon. Supporting the model, mutagenesis experiments revealed that the ΔcopS strain exhibits maximal expression of the CopRS regulon, lower intracellular Cux+ levels, and increased Cu tolerance compared to wild-type cells. The invariant phosphoacceptor residue Hisx235 of CopS was not required for the phosphatase activity itself but was necessary for its Cu dependency. To sense the metal, the periplasmic domain of CopS binds two Cux+ ions at its dimeric interface. Homology modeling of CopS based on CusS structure (four Agx+ binding sites) clearly supports the different binding stoichiometries in the two systems. Interestingly, CopS binds Cux+/2+ with 3×10x-14 M affinity, pointing to the absence of free (hydrated) Cux+/2+ in the periplasm.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
COPPER
dc.subject
HOMEOSTASIS
dc.subject
PERIPLASM
dc.subject
PSEUDOMONAS AERUGINOSA
dc.subject
TWO-COMPONENT REGULATORY SYSTEMS
dc.subject.classification
Biología Celular, Microbiología
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
The Two-Component System CopRS Maintains Subfemtomolar Levels of Free Copper in the Periplasm of Pseudomonas aeruginosa Using a Phosphatase-Based Mechanism
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-09-06T21:01:04Z
dc.identifier.eissn
2379-5042
dc.journal.volume
5
dc.journal.number
6
dc.journal.pagination
1-15
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington DC
dc.description.fil
Fil: Novoa Aponte, Lorena. Worcester Polytechnic Institute. Departmen Of Chemistry And Biochemistry; Estados Unidos
dc.description.fil
Fil: Xu, Cheng. Worcester Polytechnic Institute. Departmen Of Chemistry And Biochemistry; Estados Unidos
dc.description.fil
Fil: Soncini, Fernando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil
Fil: Argüello, José M.. Worcester Polytechnic Institute. Departmen Of Chemistry And Biochemistry; Estados Unidos
dc.journal.title
mSphere
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://msphere.asm.org/lookup/doi/10.1128/mSphere.01193-20
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/mSphere.01193-20
Archivos asociados