Variable sizes of Escherichia coli chemoreceptor signaling teams

Abstract

Like many sensory receptors, bacterial chemotaxis receptors form clusters. In bacteria, large‐scale clusters are subdivided into signaling teams that act as ‘antennas’ allowing detection of ligands with remarkable sensitivity. The range of sensitivity is greatly extended by adaptation of receptors to changes in concentrations through covalent modification. However, surprisingly little is known about the sizes of receptor signaling teams. Here, we combine measurements of the signaling response, obtained from in vivo fluorescence resonance energy transfer, with the statistical method of principal component analysis, to quantify the size of signaling teams within the framework of the previously successful Monod–Wyman–Changeux model. We find that size of signaling teams increases 2‐ to 3‐fold with receptor modification, indicating an additional, previously unrecognized level of adaptation of the chemotaxis network. This variation of signaling‐team size shows that receptor cooperativity is dynamic and likely optimized for sensing noisy ligand concentrations. ### Synopsis Bacterial chemotaxis is a much‐studied model for how small organisms sense chemicals in their environment and process information. The chemotaxis network includes membrane‐bound receptors with different chemical specificities, flagellated rotary motors, and a network that transduces signals from the receptors to the motors, allowing bacteria to swim toward nutrient chemicals and away from toxic chemicals. The bacterial chemotaxis network is well studied, and involves autophosphorylation of the receptor‐bound kinase CheA upon stimulation by receptors, followed by phospho‐transfer to the diffusible response regulator CheY. Once phosphorylated, CheY molecules can bind to the motors favoring brief changes from counterclockwise to clockwise rotation, which induce the cell to tumble and change direction. The result is longer swimming runs when cells are moving in a favorable direction. Furthermore, cells can adapt the kinase activity (and therefore the motor behavior) by covalent modification/demodification of the chemoreceptors by the enzymes CheR/CheB. Importantly, in the bacterium Escherichia coli thousands of chemoreceptors form large polar and lateral clusters composed of trimers of receptor dimers. In these large clusters, receptors are thought to interact beyond trimers of dimers to form larger receptor signaling teams ([Box 1][1]). These receptor signaling teams lead to remarkable sensitivity to changes in chemical concentration, the ability to integrate multiple chemical signals, and precise adaptation to persistent stimulation by chemical ligands. Here, we report the discovery of a new level of organization and adaptation. On the basis of our new in vivo FRET data, the size of receptor signaling teams increases by up to a factor of three with receptor modification, such as that occurs during adaptation to an attractant. Our analysis establishes a powerful approach to correlated noise based on principal component analysis (PCA) that is widely applicable to quantitative data sets. Specifically, PCA is used to obtain tight confidence intervals on important quantities such as the size of receptor signaling teams. Finally, we present a theory that the observed variation in signaling‐team size is a novel adaptive mechanism to optimally measure noisy chemical concentrations. Mol Syst Biol. 4: 211 [1]: #boxed-text-3