Prototypical two-component signal transduction systems comprises a sensor histidine kinase (HK) receptor and a response regulator (RR). Input signals induce sensor HK autophosphorylation, and the subsequent transfer of the phosphoryl-group to the RR. Upon receiving the phosphoryl-group, the RR triggers an adaptive response, often at the transcriptional level. To gain insights into how the autokinase and phosphotransferase activities of the sensor HK are coordinated, we solved structures of the catalytic core domains of the prototypical CpxA-CpxR system [1]. Our data suggest a concerted switch -involving large-scale domain motions- by which autophosphorylation and phosphotransfer reactions are allosterically coupled.