How Signals Are Heard during Bacterial Chemotaxis: Protein-Protein Interactions in Sensory Signal Propagation

Chemotaxis is a mechanism by which bacteria efficiently and rapidly respond to changes in the chemical composition of their environment, approaching chemically favorable environments and avoiding unfavorable ones. This behavior is achieved by integrating signals received from receptors that sense the environment and modulating the direction of flagellar rotation accordingly (for reviews, see references 39, 43, and 100). Early studies in the modern era, initiated some 4 decades ago (1), uncovered the behavioral response of cells to changes in the chemical composition of their environment and the correlation between flagellar rotation and the swimming mode of the cells. They also identified most of the gene products involved in chemotaxis (for reviews, see references 50 and 56). The mode of signal transduction began to be understood only in the mid-1980s, when the possibilities of electrical signaling and a direct interaction between the receptors and flagella were eliminated (for a review, see reference 41). The possibility of indirect interaction between the receptors and flagella via a protein that is activated by the receptors and inactivated as it diffuses through the cytoplasm was then raised (96). Subsequently, sequential transient phosphorylation of chemotaxis proteins was found to be a key process in signal transduction (for a review, see reference 25). During the last decade, it was established that the signal in bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium is transduced via protein-protein interactions. These interactions have been extensively studied, contributing greatly to the elucidation of the chemotaxis-signaling cascade. The chemotactic response in bacteria such as E. coli and Salmonella serovar Typhimurium is accomplished by signal transmission between two supramolecular complexes—the receptor complexes, located mainly at the pole(s) of the cell, and the flagellar-motor complexes (usually 5 to 10 complexes per cell), randomly distributed around the cell and embedded within the cell membrane. A messenger protein, CheY, shuttles back and forth between the complexes and transduces the signal from the receptors to the flagella (Fig. 1). The interaction of this messenger protein with the flagellar-motor supramolecular complex increases the probability of shifting the direction of flagellar rotation from the default direction, counterclockwise (CCW), to clockwise (CW) (for a review see reference 38). The consequence of CW rotation is an abrupt turning motion (tumbling), after which (when the default direction resumes) the cell swims in a new direction. Here we review the protein-protein interactions involved in chemotactic signaling, including interactions within the supramolecular complexes, interactions between the complexes and the messenger protein CheY, and interactions between CheY and the proteins that regulate its signaling state. Interactions involved in the signaling pathway leading to adaptation will also be reviewed. We will mainly focus on functional aspects of the interactions. The reader is referred to references 13, 35, 43, 54, and 81 for more-detailed structural aspects. Because this is a minireview, the reference list is incomplete. Whenever possible, reference is made to reviews or papers that provide access to the original literature.