X-ray protein crystallography reveals unique functions and components in a phospho-signaling system that controls metabolism and virulence of Mycobacterium tuberculosis

MARÍA-NATALIA LISA

Congreso; 30th edition of LNLS Annual Users Meeting (RAU); 2020

Brazilian Synchrotron Light Laboratory (LNLS), part of the Brazilian Center for Research in Energy and Materials (CNPEM)

Reversible protein phosphorylation has evolved as a ubiquitous molecular mechanism of protein regulation. Phosphorylation on serine (Ser), threonine (Thr) and tyrosine (Tyr) is central to bacterial physiology and pathogenesis, and the corresponding phospho-systems share similarities to those in eukaryotes [1]. However, as novel functions and components of bacterial O-phosphorylation are identified, distinct differences between pro- and eukaryotic phospho-signaling systems become apparent that could be exploited for drug development. In this presentation I am going to outline recent advances in the study of the signal transduction pathway that involves the Ser/Thr protein kinase PknG [2-4], which senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis [5,6] and has a conserved function in amino acid homeostasis in diverse Actinobacteria [7]. In addition, I will present views and objectives of PlaBEM, the Argentinian Platform for Metabolomics and Structural Biology, regarding X-ray protein crystallography projects. We offer access to our crystallization facilities, coordinate data acquisition sessions in synchrotrons, and organize courses/workshops aimed at training young scientists in integrative structural biology. The results to be presented constitute the basis of future proposals for the use of the Manacá beamline of the Sirius synchrotron. [1] Sherman DR and Grundner C. Mol Microbiol 94, 231-241 (2014); [2] O´Hare HM et al. Mol Microbiol 70, 1408-1423 (2008); [3] Lisa MN et al. Structure 23, 1039-1048 (2015); [4] Gil M et al. J Proteomics 192, 321-333 (2019); [5] Rieck B et al. PLoS Pathog 13, e1006399 (2017); [6] York A. Nat Rev Microbiol 15, 383-383 (2017); [7] Niebisch A J et al. J Biol Chem 281, 12300-12307 (2006).