Bacterial chemoreceptors and chemoeffectors

Abstract

Bacteria use chemotaxis signaling pathways to sense environmental changes. Escherichia coli chemotaxis system represents an ideal model that illustrates fundamental principles of biological signaling processes. Chemoreceptors are crucial signaling proteins that mediate taxis toward a wide range of chemoeffectors. Recently, in deep study of the biochemical and structural features of chemoreceptors, the organization of higher-order clusters in native cells, and the signal transduction mechanisms related to the on-off signal output provides us with general insights to understand how chemotaxis performs high sensitivity, precise adaptation, signal amplification, and wide dynamic range. Along with the increasing knowledge, bacterial chemoreceptors can be engineered to sense novel chemoeffectors, which has extensive applications in therapeutics and industry. Here we mainly review recent advances in the E. coli chemotaxis system involving structure and organization of chemoreceptors, discovery, design, and characterization of chemoeffectors, and signal recognition and transduction mechanisms. Possible strategies for changing the specificity of bacterial chemoreceptors to sense novel chemoeffectors are also discussed.

Fig. 1

The chemotaxis transduction network in E. coli [1, 5]. Several types of chemoreceptors (in different colors and shapes) specifically sense different kinds of chemoeffectors in the environment, including attractants (red spots or yellow triangles), repellents (blue squares), antagonists (green diamonds or purple ovals) and other environmental effectors (blue arrows). One trimer of receptor dimers, one CheW protein, and one CheA monomer (the other CheA monomer is shown as a dashed line) are shown in the figure. Receptor methylation sites are shown as white (unmethylated) or black (methylated) circles. The phosphoryl groups are shown as yellow stars

Fig. 2

Illustration of a conventional chemoreceptor homodimer and the mechanism of chemoeffector binding and signaling. a Structural features of a conventional chemoreceptor homodimer in E. coli. The specific features and motifs are noted to the sides of the dimer. b The predicted interactions of Tar periplasmic sensing domain with attractant l-aspartate, cis-PDA, and antagonist CHDCA. The helices of receptor periplasmic sensing domains are shown as white cylinders. The binding molecules are shown as balls and sticks and the key interaction residues are shown as sticks. Oxygen atoms are shown in red and nitrogen atoms are shown in blue. Hydrogen bonds are indicated by black dashed lines. The interactions between the N–H group of attractants with the main-chain carbonyls of Tyr149 (Y149) and/or Gln152 (Q152) are crucial for eliciting chemotactic signals, which contribute to binding and signaling. The interactions of carboxyl groups of molecules with Arg64 (R64), Arg69′ (R69′) and Arg73′ (R73′) mainly contribute to binding [40]. a Drawn based on Refs. [5, 30], b drawn based on Ref. [40]

Fig. 3

Illustration of the assembly of a chemosensory array. Only P3 and P5 domains of CheA are shown in the figure. The core functional unit of signaling complexes involves two trimers of receptor dimers interacting with two CheW proteins and one CheA dimer [41]. The CheA P5 domains and CheW form rings to link trimers of receptor dimers into hexagons. The CheA P3 domains link hexagons to form extended sensory arrays [44, 46]. This figure is drawn based on Refs. [44, 46, 47]

Fig. 4

Mechanisms of transmembrane signaling for E. coli chemoreceptors. a Mechanism of piston displacements [–113], b mechanism of scissoring motions [12, 13, 15], c mechanism of rotation of helices [114], and d mechanism of supercoil unwinding of helices [115]. The helices of receptor periplasmic sensing domains are shown as blue cylinders. The attractants are shown in red

Fig. 5

Three strategies for changing the specificity of chemoreceptors. The rational design strategy starts with the full understanding of receptor structures, mechanisms, and functions. Residues that may bind to a novel chemoeffector are predicted rationally. The variant genes are obtained by site-directed mutagenesis and then expressed in E. coli [40, 142]. The directed evolution strategy needs mutant gene libraries that can be prepared by random mutagenesis or gene fragment recombination [–143]. Libraries of E. coli variants are obtained after gene transformation and expression. Making hybrid chemoreceptors is another strategy to change the ligand specificity. Two receptor genes can be fused together according to the sequence conservation [141]. The non-native periplasmic sensing domains in hybrid receptors enable E. coli to sense novel ligands. The methods for selecting desirable E. coli variants that can sense novel chemoeffectors are various, such as capillary assay [60], agar plate assay [143], microfluidic assay [40], and FRET assay [68]. The three strategies can be successively used in combination to optimize the desired function