X-ray protein crystallography as a tool for the study of bacterial signal transduction

MARÍA-NATALIA LISA

Buenos Aires

Congreso; XIV reunión anual de la Asociación Argentina de Cristalografía; 2018

Asociación Argentina de Cristalografía

Cells use signal transduction to sense the environment and regulate central processes in response to environmental stimuli. Reversible protein phosphorylation has evolved as a ubiquitous molecular mechanism of protein regulation. Indeed, the flow of information from the outside to the inside of bacterial cells is largely directed by histidine (His) kinases in two component systems and by eukaryotic-like protein kinases. Work in Mycobacterium tuberculosis (Mtb) reinforces the idea that phosphorylation on serine (Ser), threonine (Thr) and tyrosine (Tyr) is central to bacterial physiology and pathogenesis, and that the corresponding phospho-systems share similarities to those in eukaryotes (Sherman and Grundner, 2014, Mol Microbiol). However, as novel functions and components of bacterial O-phosphorylation are identified, distinct differences between pro- and eukaryotic phospho-signaling systems become apparent, revealing specific protein:protein interfaces that could be exploited for the development of selective drugs with unconventional modes of action. In this talk I am going to present recent advances in the understanding of the signal transduction pathway involving PknG (O´Hare et al, 2008, Mol Microbiol), a unique multi-domain Ser/Thr protein kinase (Scherr et al, 2007, PNAS; Lisa et al, 2015, Structure) that senses amino acid availability to control metabolism and virulence of Mtb (Rieck et al, 2017, Plos Pathogens), and which has a conserved function in amino acid homeostasis amongst the Actinobacteria (Cowley et al, 2004 Mol Microbiol; Niebisch et al, 2006, J Biol Chem).