Dimer asymmetry and light activation mechanism in Brucella blue-light sensor histidine kinase

JIMENA RINALDI, IGNACIO FERNÁNDEZ, HEEWHAN SHIN, GABRIELA SYCZ, SEMINI GUNAWARDANA, INDIKA KUMARAPPERUMA, JUAN M. PAZ, LISANDRO H. OTERO, MARÍA L. CERUTTI, ÁNGELES ZORREGUIETA, ZHONG REN, SEBASTIÁN KLINKE, XIAOJING YANG AND FERNANDO A. GOLDBAUM

mBio

American Society for Microbiology (ASM)

Año: 2021

The ability to sense and respond to environmental cues is essential for adaptation and survival in living organisms. In bacteria, this process is accomplished by multi-domain sensor histidine kinases that undergo auto-phosphorylation in response to specific stimuli, thereby triggering downstream signaling cascades. However, the molecular mechanism of allosteric activation is not fully understood in these important sensor proteins. Here we report the full-length crystal structure of a blue light photoreceptor LOV histidine kinase (LOV-HK) involved in light-dependent virulence modulation in the pathogenic bacterium Brucella abortus. Joint analyses of the dark and light structures determined in different signaling states have shown that LOV-HK transitions from a symmetric dark structure to a highly asymmetric light state. The initial local and subtle structural signal originated in the chromophore-binding LOV domain alters the dimer asymmetry via coiled coil rotary switch and helical bending in the helical spine. These amplified structural changes result in enhanced conformational flexibility and large-scale rearrangements that facilitate the phosphoryl transfer reaction in the HK domain.