The main signal transduction system in microorganisms is based on the use of two proteins: a sensor histidine kinase dimeric active and commonly located in the membrane, and an intracellular second messenger, called the response regulator. The signal sensor regulates the autophosphorylation of a histidine residue, and thereafter, this phosphoryl group is transferred to an aspartic acid residue of the response regulator, which, for example, migrates to the chromosome and modulate gene expression. The signal is terminated by the dephosphorylation of response regulator spontaneously or due to phosphatase activity of histidine kinase.

Using techniques of protein crystallography and X-ray diffraction, researchers at the Instituto de Biomedicina de Valencia (CSIC) have obtained the first near-atomic resolution image of a complex bacterial histidine kinase-response regulator dephosphorylation process. This structure clarifies the mechanism of the reaction and sheds light on the mechanism of histidine kinase fosfotransferencia from the regulator of the response, a reaction that is reverse to the dephosphorylation.

Moreover, the structure reveals why the couple histidine kinase-response regulator are not promiscuous, allowing to know the molecular basis of high specificity in these systems and the rationale for the design of inhibitors directed. The structure analysis led the authors to question the mechanism, considered to be universal in autophosphorylation in trans to the histidine kinase dimer, demonstrating biochemically at work that some histidine kinases can autofosforilarse in cis. Finally, the authors suggest a model of how the signal is transmitted into the extracellular bacteria.