IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Acyl-CoAs as effector molecules: understanding the transcriptional regulatory network in mycobacteria
Autor/es:
LARA J; MONDINO S; DIACOVICH L; GAGO GABRIELA; GRAMAJO H
Lugar:
Rosario
Reunión:
Congreso; Reunión Anual Nro.50 de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2014
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
Mycobacteria have two fatty acid synthases which work in concert to synthesize fatty acids and mycolic acids. We identified two transcriptional regulators essential for mycobacterial viability: MabR, which controls the expression of fasII operon genes, and FasR, which specifically binds to fas promoter region and controls the de novo fatty acid biosynthesis. The main purpose of our studies is to understand how mycobacteria exert a fine control over the biosynthesis of their membrane. The characterization of the effectors molecules that modulates the affinity of FasR and MabR for its DNA target was studied using EMSA, lacZ transcriptional fusions, SPR and in vitro transcription. In order to deeply characterize the molecular bases of MabR and FasR interaction with their corresponding DNA targets and effector molecules, we performed crystallographic experiments. In this work, we show that long-chain Acyl-CoAs are key effector molecules that coordinate the expression of the two FAS systems, by directly binding to FasR and MabR. Furthermore, rod-like crystals of MabR native protein where found in the presence of the DNA interacting probe and thin needles crystals of FasR were obtained in presence of C20-CoA. A better understanding of this complex process of regulation of lipid homeostasis in mycobacteria will greatly contribute to the development of new strategies to control this disease.