dc.creatorBelluzo, Bruno Salvador
dc.creatorAbriata, Luciano Andres
dc.creatorGiannini, Estefanía
dc.creatorMihovilcevic, Damila
dc.creatorDal Peraro, Matteo
dc.creatorLlarrull, Leticia Irene
dc.date.accessioned2022-03-16T01:48:41Z
dc.date.accessioned2022-10-15T09:46:56Z
dc.date.available2022-03-16T01:48:41Z
dc.date.available2022-10-15T09:46:56Z
dc.date.created2022-03-16T01:48:41Z
dc.date.issued2019-12
dc.identifierBelluzo, Bruno Salvador; Abriata, Luciano Andres; Giannini, Estefanía; Mihovilcevic, Damila; Dal Peraro, Matteo; et al.; An experiment-informed signal transduction model for the role of the Staphylococcus aureus MecR1 protein in β-lactam resistance; Nature Research; Scientific Reports; 9; 1; 12-2019; 19558-19572
dc.identifier2045-2322
dc.identifierhttp://hdl.handle.net/11336/153415
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4372139
dc.description.abstractThe treatment of hospital- and community-associated infections by methicillin-resistant Staphylococcus aureus (MRSA) is a perpetual challenge. This Gram-positive bacterium is resistant specifically to β-lactam antibiotics, and generally to many other antibacterial agents. Its resistance mechanisms to β-lactam antibiotics are activated only when the bacterium encounters a β-lactam. This activation is regulated by the transmembrane sensor/signal transducer proteins BlaR1 and MecR1. Neither the transmembrane/metalloprotease domain, nor the complete MecR1 and BlaR1 proteins, are isolatable for mechanistic study. Here we propose a model for full-length MecR1 based on homology modeling, residue coevolution data, a new extensive experimental mapping of transmembrane topology, partial structures, molecular simulations, and available NMR data. Our model defines the metalloprotease domain as a hydrophilic transmembrane chamber effectively sealed by the apo-sensor domain. It proposes that the amphipathic helices inserted into the gluzincin domain constitute the route for transmission of the β-lactam-binding event in the extracellular sensor domain, to the intracellular and membrane-embedded zinc-containing active site. From here, we discuss possible routes for subsequent activation of proteolytic action. This study provides the first coherent model of the structure of MecR1, opening routes for future functional investigations on how β-lactam binding culminates in the proteolytic degradation of MecI.
dc.languageeng
dc.publisherNature Research
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41598-019-55923-z
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-019-55923-z
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectStaphylococcus aureus
dc.subjectMecR1
dc.subjectbeta-lactam antibiotics
dc.titleAn experiment-informed signal transduction model for the role of the Staphylococcus aureus MecR1 protein in β-lactam resistance
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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