Conformational signaling in chemoreceptor dimers. The left-hand schematic, labeled ’Attractant response’ shows the conformational changes that convey an informational signal from one end of the chemoreceptor to the other. The right-hand schematic, labeled ’Sensory adaptation’, shows how covalent modification of an attractant-occupied receptor (methylation of specific glutamyl residues) reverses the ligand-induced conformational changes and thus mediates sensory adaptation. For clarity, a single receptor dimer is shown, embedded in the cytoplasmic membrane (light gray rectangle). As seen in the left-hand schematic, binding of an attractant chemoeffector (gray circle) to the transmembrane sensing module (green) initiates downward displacement of the signaling helix (see arrow heads on the signaling helix of the transmembrane sensing module) []. This movement generates an as-yet undefined conformational change in the signal conversion module (gray), which shifts its signaling state. This shift in turn weakens subunit interactions (symbolized by heavy arrows pointing away from the interface of subunit interaction) in the kinase control module (blue), resulting in increased flexibility, twisting and/or bending of the receptor molecule [,–]. These changes, either directly or through effects on the trimer [,,], deactivate coupled CheA kinase molecules leading to a counter-clockwise motor response. The same conformational changes also increase the propensity of the kinase control module for methylation and decrease its propensity for demethylation. The ligand-induced kinase inhibition decreases the level of active, phosphorylated demethylating enzyme CheB, thereby further increasing the number of methylated adaptation sites (black circles in the kinase control domain) at the expense of demethylated adaptation sites (white circles in the kinase control domain). Increased methylation terminates the motor response by reversing the attractant-triggered conformational changes []. Methylation strengthens subunit interactions (symbolized by heavy arrows pointing toward the interface of subunit interaction) in the kinase control domain, reducing its flexibility and activating coupled CheA kinases []. The reduced dynamic motion and strengthened subunit interactions of the kinase control domain also reverse the signaling state of the signal conversion module and thus cause upward movement of the signaling helix, reversing the conformational change of the transmembrane sensing module and influencing the conformation of the ligand-binding site []. Overall, the effects of increased methylation counteract the conformational and functional effects of ligand occupancy, re-establishing the conformational and signaling state of the chemoreceptor before ligand occupancy.