Functional and structural characterization of the light-activated transduction pathway from Brucella (comunicación oral)

JIMENA RINALDI; GABRIELA SYCZ; MARIANA GALLO; SEBASTIÁN KLINKE; DANIEL O. CICERO; GASTÓN PARIS; FERNANDO A. GOLDBAUM

Puerto Varas

Congreso; XII PABMB Congress; 2013

Panamerican Association for Biochemistry and Molecular Biology

Bacteria use sensor histidine kinases (HK) to detect environmental signals and to induce the corresponding metabolic adaptation. Upon detection of the environmental signal, HK autophosphorylates in a conserved histidine residue. The phosphoryl group is transferred to the second component, a response regulator (RR), that typically binds DNA and activates the transcription of target genes. In previous work we have identified a LOV domain containing HK protein from B. abortus (LOVHK) that is important for the virulence of the bacteria. This protein contains an N-terminal photosensory LOV domain, a PAS domain and a C-terminal histidine kinase domain. The LOV domain binds FMN as cofactor and upon illumination with blue-light performs a self-contained photocycle that activates the autophosphorylation of the HK domain. Structural analysis of LOV domain shown that a beta sheet and a C-terminal alpha helix from the LOV domain are the key structural elements involved in the mechanism of signal transduction to other protein domains. The crystal structure of HK domain suggest that this domain suffer large conformational changes involving the N-terminal alpha helices. Our analysis points to the alpha helices connecting the different domains as the key elements for intramolecular signal transduction. This mechanism increase the autophosphorylation which initiates a signal transduction pathway that controls the expression of relevant genes for Brucella virulence.