Crystallographic study of the multi-domain Brucella blue light-activated histidine kinase LOV-HK (Conferencia Semiplenaria)

IGNACIO FERNÁNDEZ; LISANDRO OTERO; SEBASTIÁN KLINKE; HEEWHAN SHIN; MARÍA L. CERUTTI; FERNANDO A. GOLDBAUM; JIMENA RINALDI; SEMINI GUNAWARDANA; XIAOJING YANG

Bucaramanga

Congreso; IV Meeting of the Latin American Crystallographic Association; 2019

Latin American Crystallographic Association (LACA)

The pathogenic bacterium Brucella abortus codes for a multi-domain cytoplasmic histidine kinase called LOV-HK, which is a key blue light-activated virulence factor in this microorganism, and a member of a two-component system involved in the bacterial general stress response. It has been shown that the exposure of Brucella to visible light results in higher level of bacterial replication in the host cells, and that this effect is mediated by LOV-HK. Brucella LOV-HK is a dimeric protein that comprises an N-terminal blue-light sensor LOV domain, a central PAS domain with unknown function and a C-terminal histidine kinase HK domain. The mechanism of activation of this protein, and of sensor HKs in general, is not fully understood. To address this challenge, we solved the crystal structure of several multi-domain constructs of the protein in dark and illuminated states, including the full-length light-activated version at 3.25 A resolution. The analysis and comparison of these three-dimensional models allowed us to propose a model for the activation of this crucial system in Brucella, which will be presented in this talk.