The successful design and construction of TCRS provide a better understanding of the system to obtain a chimeric TCRS customized for achieving a desired input/output. The HK domain, which has a variety of signal recognition capabilities, may be used to couple or shuffle a broad range of input signals to the appropriate output responses through a conserved phosphotransfer process. This shuffling can be achieved by cross-linking the domains of evolutionarily distinct TCRSs, and a chimeric TCRS with the desired sensing ability can be obtained. Most of the domain shuffling required for rational design of chimeric proteins is between HKs and rarely between RRs. At present, several research groups have successfully constructed a chimeric two-component sensor protein by fusing the HK domain to the sensory domain of another kinase or a completely unrelated protein. These studies improve our understanding of the molecular events that occur during signal transduction across membranes in these organisms.