Structural insights into the signal transduction mechanism of the thermosensor histidine-kinase DesK from Bacillus subtilis

ALBANESI, DANIELA; MARTÍN, MARIANA; TRAJTENBERG, FELIPE; MANSILLA, MARÍA CECILIA; HAOUZ, AHMED; ALZARI, PEDRO; DE MENDOZA, DIEGO; BUSCHIAZZO, ALEJANDRO

San Diego Ca USA

Congreso; 15th International Conference on Bacilli. 5th Conference on Functional Genomics of Gram-positive Microorganisms; 2009

The Scripps Institute

Temperature sensing is essential for the survival of living cells. A major challenge is to understand how thermal information is processed by a biological thermometer to optimize cellular functions. In bacteria, the most studied system leading to thermal adaptation is the Des pathway of Bacillus subtilis which is composed of the DesK/DesR two-component system (TCS) and D5-Des, a D5-acyl desaturase encoded by the des gene. The DesK/DesR TCS functions as a molecular thermosensor that responds to temperature variations to regulate fatty acid desaturation metabolism. Induction of the Des pathway is brought about by the ability of the histidine kinase DesK to assume different signaling states in response to variations in membrane fluidity. An increase in the proportion of ordered membrane lipids favors a kinase-dominant state of DesK, which undergoes autophosphorylation and then transfers the phosphate to the response regulator DesR. DesR-P binds to the des promoter inducing des transcription. Once synthesized, Ä5-Des introduces double bonds in the acyl chains of membrane lipids decreasing the transition temperature of the phospholipids. A more fluid membrane favors the phosphatase activity of DesK on DesR-P turning off des transcription. Through a structural and biochemical approach we show: i) that temperature modulates the kinase and phosphatase activities of DesK by a mechanism requiring the integrity of the sensor domain, comprised by the transmembrane segments and ii) that stimuli propagate across the membrane to promote helical rotation in the four-helix bundle modulating its association with the ATP-binding domain to control the activities of the sensor protein.