Structural Basis of Response Regulator Function

Response regulators function as the output components of two-component systems, which couple the sensing of environmental stimuli to adaptive responses. Response regulators typically contain conserved receiver (REC) domains that function as phosphorylation-regulated switches to control the activities of effector domains that elicit output responses. This modular design is extremely versatile, enabling different regulatory strategies tuned to the needs of individual signaling systems. This review summarizes structural features that underlie response regulator function. An abundance of atomic resolution structures and complementary biochemical data have defined the mechanisms for response regulator enzymatic activities, revealed trends in regulatory strategies utilized by response regulators of different subfamilies, and provided insights into interactions of response regulators with their cognate histidine kinases. Among the hundreds of thousands of response regulators identified, variations abound. This article provides a framework for understanding structural features that enable function of canonical response regulators and a basis for distinguishing noncanonical configurations.