Internal Sense of Direction: Sensing and Signaling from Cytoplasmic Chemoreceptors

Abstract

SUMMARY Chemoreceptors sense environmental signals and drive chemotactic responses in Bacteria and Archaea . There are two main classes of chemoreceptors: integral inner membrane and soluble cytoplasmic proteins. The latter were identified more recently than integral membrane chemoreceptors and have been studied much less thoroughly. These cytoplasmic chemoreceptors are the subject of this review. Our analysis determined that 14% of bacterial and 43% of archaeal chemoreceptors are cytoplasmic, based on currently sequenced genomes. Cytoplasmic chemoreceptors appear to share the same key structural features as integral membrane chemoreceptors, including the formations of homodimers, trimers of dimers, and 12-nm hexagonal arrays within the cell. Cytoplasmic chemoreceptors exhibit varied subcellular locations, with some localizing to the poles and others appearing both cytoplasmic and polar. Some cytoplasmic chemoreceptors adopt more exotic locations, including the formations of exclusively internal clusters or moving dynamic clusters that coalesce at points of contact with other cells. Cytoplasmic chemoreceptors presumably sense signals within the cytoplasm and bear diverse signal input domains that are mostly N terminal to the domain that defines chemoreceptors, the so-called MA domain. Similar to the case for transmembrane receptors, our analysis suggests that the most common signal input domain is the PAS (Per-Arnt-Sim) domain, but a variety of other N-terminal domains exist. It is also common, however, for cytoplasmic chemoreceptors to have C-terminal domains that may function for signal input. The most common of these is the recently identified chemoreceptor zinc binding (CZB) domain, found in 8% of all cytoplasmic chemoreceptors. The widespread nature and diverse signal input domains suggest that these chemoreceptors can monitor a variety of cytoplasmically based signals, most of which remain to be determined.

The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress

“…These studies, however, were done in wild-type cells that possess multiple chemoreceptors. Our work shows that a soluble chemoreceptor can be sufficient to organize a signaling complex, consistent with the observation that some prokaryotes have only soluble chemoreceptors (1). Polar localization of chemoreceptors is achieved using a variety of mechanisms, including stochastic self-assembly, the use of polar landmark proteins, and ParA orthologues (52).…”

“…Cytoplasmic chemoreceptors are relatively understudied but represent 14% of bacterial and 43% of archaeal chemoreceptors (1). As a group, cytoplasmic chemoreceptors are reported to mediate tactic responses to diverse conditions, including to increased cellular energy stores (2,3), redox conditions (4,5), and metabolites (6), although significant gaps remain in our understanding of what they sense and how they function (1). One such cytoplasmic chemoreceptor is Helicobacter pylori TlpD.…”

“…TlpD additionally has a C-terminal zinc-binding domain (CZB) (9,10), which is the second most prevalent domain found in cytoplasmic chemoreceptors (1). Numerous cytoplasmic chemoreceptors contain a CZB domain and thus share a domain structure with TlpD (1,9). Chemoreceptors, like TlpD, are widespread and found in many bacterial genera, including gastric and nongastric Helicobacter species.…”

“…TlpD possesses the canonical chemoreceptor domain, called MA or methylaccepting chemotaxis receptor protein (MCP) signal, which typically interacts with the signal transduction proteins CheW and CheA. TlpD additionally has a C-terminal zinc-binding domain (CZB) (9,10), which is the second most prevalent domain found in cytoplasmic chemoreceptors (1). Numerous cytoplasmic chemoreceptors contain a CZB domain and thus share a domain structure with TlpD (1,9).…”

“…It contains typical core signaling proteins, the CheA kinase, the CheW coupling protein, and the CheY response regulator, all of which are required for chemotaxis (1,12,13). H. pylori encodes three transmembrane chemoreceptors called TlpA (HP0099), TlpB (HP0103), and TlpC (HP0082) (7,8,12,14).…”