Sensor domains of two-component regulatory systems

Abstract

Two-component systems regulate crucial cellular processes in microorganisms, and each comprises a homodimeric histidine kinase receptor and a cytoplasmic response regulator. Histidine kinases, often membrane associated, detect environmental input at sensor domains and propagate resulting signals to catalytic cytoplasmic transmitter domains. Recent studies on the great diversity of sensor domains reveal patterns of domain organization and biochemical properties that provide insight into mechanisms of signaling. Despite the enormous sequence variability found within sensor input domains, they fall into a relatively small number of discrete structural classes. Subtle rearrangements along a structurally labile dimer interface, in the form of possible sliding or rotational motions, are propagated from the sensor domain to the transmitter domain to modulate activity of the receptor.

Figure 1. Histidine kinase Domain Organization

A schematic showing some basic examples of sensor domain organization in context with the full length histidine kinase receptor: (A) The sensor domain is often formed as a folded extracellular loop between usually two transmembrane segments in a membrane-spanning histidine kinase. (B) The sensor domain may be embedded within the membrane, composed from transmembrane helices as if having a truncated extracellular loop truncated to a stub. (C) The cytoplasmic sensor domain may be located N-terminal to two or more transmembrane segments in a membrane-anchored histidine kinase. (D) The cytoplasmic sensor domain may be located C-terminal to two or more transmembrane segments in a membrane-anchored histidine kinase. (E) The cytoplasmic sensor domain may reside N-terminal to the C-terminal transmitter domain in a soluble histidine kinase that lacks transmembrane segments. Transmembrane segments designated TM1 and TM2 may be composed of more than one transmembrane segment, but always an odd number.

Figure 2. Sensor Domain Insertions

Ribbon diagrams of (A) PDC sensors DcuS and DctB, and (B) all-alpha sensors NarX and Tors showing domain insertions in the fold. Non-protein moieties are shown in ball-and-stick representation with carbon in yellow, oxygen in red, and calcium in magenta.

Figure 3. Dimeric Sensor Domains with Modeled Transmembrane Helices

Dimeric sensor domain structures of DcuS and NarX have been modeled with transmembrane helices based on those of the phototaxis transducer [30]. Drawings are as ribbon diagrams with residues of the sensor domains colored green and blue and the modeled transmembrane residues colored grey. Non-protein moieties malate and nitrate, bound to DcuS and NarX respectively, are depicted in ball-and-stick representation. Putative plane of the lipid bilayer is depicted as grey lines.