title: In depth analysis of the mechanism of action of metal-dependent sigma factors: characterization of CorE2 from Myxococcus xanthus.
abstract: Extracytoplasmic function sigma factors represent the third pillar of signal-transduction mechanisms in bacteria. The variety of stimuli they recognize and mechanisms of action they use have allowed their classification into more than 50 groups. We have characterized CorE2 from Myxococcus xanthus, which belongs to group ECF44 and upregulates the expression of two genes when it is activated by cadmium and zinc. Sigma factors of this group contain a Cys-rich domain (CRD) at the C terminus which is essential for detecting metals. Point mutations at the six Cys residues of the CRD have revealed the contribution of each residue to CorE2 activity. Some of them are essential, while others are either dispensable or their mutations only slightly affect the activity of the protein. However, importantly, mutation of Cys174 completely shifts the specificity of CorE2 from cadmium to copper, indicating that the Cys arrangement of the CRD determines the metal specificity. Moreover, the conserved CxC motif located between the σ2 domain and the σ4.2 region has also been found to be essential for activity. The results presented here contribute to our understanding of the mechanism of action of metal-dependent sigma factors and help to define new common features of the members of this group of regulators.
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Marcos-Torres
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Pérez
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Gómez-Santos
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Moraleda-Muñoz
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain jdorado@ugr.es.
authors.forename: José
authors.initials: J
authors.lastname: Muñoz-Dorado
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D002104:Cadmium / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003545:Cysteine / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D009154:Mutation; D016941:Myxococcus xanthus / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; D015534:Trans-Activators; D002104:Cadmium; D003300:Copper; D015032:Zinc; D003545:Cysteine