Signaling and sensory adaptation in Escherichia coli chemoreceptors: 2015 update

Abstract

Motile Escherichia coli cells track gradients of attractant and repellent chemicals in their environment with transmembrane chemoreceptor proteins. These receptors operate in cooperative arrays to produce large changes in the activity of a signaling kinase, CheA, in response to small changes in chemoeffector concentration. Recent research has provided a much deeper understanding of the structure and function of core receptor signaling complexes and the architecture of higher-order receptor arrays, which, in turn, has led to new insights into the molecular signaling mechanisms of chemoreceptor networks. Current evidence supports a new view of receptor signaling in which stimulus information travels within receptor molecules through shifts in the dynamic properties of adjoining structural elements rather than through a few discrete conformational states.

Keywords: cooperative network; kinase control; transmembrane signaling.

Figure 1. Signal transmission in chemoreceptor dimers

(A) Architectural features of receptor molecules. Cylindrical segments represent alpha-helical secondary structures, drawn approximately to scale. The two protomers of the homodimer are shown in different shades of blue. Each protomer contains four adaptational modification sites (gray and white circles) common to Tar and Tsr. Gray sites are synthesized as glutaminyl residues and subsequently converted to glutamyl residues by CheB action; white sites are synthesized as glutamyl residues. Sites on the two helices in back are shown as dashed, white outlines. White rectangles in the flexible bundle region represent glycine hinge residues. The 4-helix bundle of the cytoplasmic kinase control domain ends with an unstructured linker segment at the C-terminus of each subunit (thin wavy line). A pentapeptide sequence (NWETF) at the very C-terminus provides a binding site for the CheR and CheB modification enzymes of the sensory adaptation system. (B) Structure of the TM bundle-control cable-HAMP region of Tar and Tsr. The transmembrane (TM) helices form a 4-helix bundle with interactions between the TM1 and TM1' helices at the dimer interface. Attractant stimuli promote ~2 Å inward piston movement of one of the TM2 helices, which is transmitted through the five control cable residues to modulate the structural stability of the HAMP domain. The first two control cable residues of Tar and Tsr play critical roles in transmembrane signaling, whereas the sidechain character of the other control cable residues has little effect on function. (C) Dynamic-bundle model of the signaling interplay between the HAMP and MH bundles. The model [41] proposes that the packing stabilities of the HAMP and methylation helix (MH) bundles are coupled in opposition and vary over a range of conformations. Light gray horizontal lines represent weak inter-helix packing forces; black lines represent strong bundle-packing forces. The sensory adaptation system (CheR and CheB enzymes) also modulates MH bundle stability. Unmodified adaptation sites (white circles) destabilize MH packing and promote kinase-off output. Methylated sites (black circles) stabilize MH packing and promote kinase-on output. (D) The cytoplasmic tip of Tsr showing residues that probably influence tip conformation and dynamics. These structural features are conserved in Tar and most other MCPs. Helices are shown as backbones, with glycine hinge residues in space-fill mode. Side-chain atoms of residues F396 and E391 at the tip are shown as transparent spheres enclosing sticks. Note the stacking interaction of the F396 sidechains in the interior of the 4-helix bundle and the solvent-exposed orientation of E391.

Figure 2. Receptor core complexes and arrays

The same fill color conventions for the various signaling components and domains are used in all panels. White lines in panels A–C separate the protomers of homodimeric molecules. (A) Core complex, the minimal unit of receptor signaling. Two receptor trimers of dimers and two CheW molecules are needed to activate and control a CheA dimer. The trimers can contain receptors with different detection specificities (dark green and dark blue). CheA protomers have five domains: P1 (phosphorylation site); P2 (CheB and CheY binding); P3 (dimerization domain); P4 (catalysis, P1 and ATP binding); P5 (receptor/CheW coupling and activity control). A binding interaction between CheW and its CheA-P5 paralog (black circle) is critical for core complex assembly. (B) Cross-section through the CheA-P5/CheW baseplate of a core complex viewed from the cytoplasmic membrane toward the protein interaction tips of the receptors. Black symbols indicate protein-protein contacts involved in core complex assembly and function: P5-receptor (squares); CheW-receptor (rectangles); P5 [subdomain 1]-CheW [subdomain 2] (circles); trimer contacts between inner subunits of receptor dimers (triangles). Parallel black lines between the P5 and P3 domains of CheA indicate the linkers flanking the P4 domain, a likely route for signaling conformational changes in the core complex. (C) Signaling connections between core complexes in the receptor array that may confer response amplification. Red squares indicate P3-P3' interactions that could transmit allosteric signals between CheA protomers. Red circles denote interface 2 interactions between P5 (subdomain 2) and CheW (subdomain 1) that could transmit allosteric signals through hexagonal P5-CheW rings. (D) Proposed organization of core complexes in the receptor array. In addition to hexagonal P5-CheW rings (solid black line), hexagonal rings of CheW might also exist (broken black line).