The protein scaffold calibrates metal specificity and activation in MerR sensors

MerR metalloregulators are the central components of many biosensor platforms designed to report metal contamination. However, most MerR proteins are non-specific. This makes it difficult to apply these biosensors in the analysis of real environmental samples. On-demand implementation of molecular e...

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Detalles Bibliográficos
Autores: Mendoza Fernández, Julián Ignacio, Lescano, Julian, Soncini, Fernando Carlos, Checa, Susana Karina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/217603
Acceso en línea:http://hdl.handle.net/11336/217603
Access Level:acceso abierto
Palabra clave:MerR
TRANSCRIPTIONAL REGULATOR
SYNTHETIC SENSOR
METAL RECOGNITION
BIOSENSOR BACTERIA
PROTEIN ENGINEERING
REPORTER GENE
https://purl.org/becyt/ford/2.8
https://purl.org/becyt/ford/2
Descripción
Sumario:MerR metalloregulators are the central components of many biosensor platforms designed to report metal contamination. However, most MerR proteins are non-specific. This makes it difficult to apply these biosensors in the analysis of real environmental samples. On-demand implementation of molecular engineering to modify the MerR metal preferences is innovative, although it does not always yield the expected results. As the metal binding loop region (MBL) of these sensors has been proposed to be the major modulator of their specificity, we surgically switched this region for that of well-characterized specific and non-specific homologues. We found that identical modifications in different MerR proteins result in synthetic sensors displaying particular metal-detection patterns that cannot be predicted from the nature of the assembled modules. For instance, the MBL from a native Hg(II) sensor provided non-specificity or specificity toward Hg(II) or Cd(II) depending on the MerR scaffold into which it was integrated. These and other evidences reveal that residues outside the MBL are required to modulate ion recognition and transduce the input signal to the target promoter. Revealing their identity and their interactions with other residues is a critical step toward the design of more efficient biosensor devices for environmental metal monitoring.