Abstract
Two-component signaling circuits (TCSs) govern the majority of environmental, pathogenic and industrial processes undertaken by bacteria. Therefore, controlling signal output from these circuits in a stimulus-independent manner is of central importance to synthetic microbiologists. Aromatic tuning, or repositioning the aromatic residues commonly found at the cytoplasmic end of the final TM helix has been shown to modulate signal output from the aspartate chemoreceptor (Tar) and the major osmosensor (EnvZ) of Escherichia coli. Aromatic residues are found in a similar location within other bacterial membrane-spanning receptors, suggesting that aromatic tuning could be harnessed for a wide-range of applications. Here, a brief synopsis of the data underpinning aromatic tuning, the initial successes with the method and the inherent advantages over those previously employed for modulating TCS signal output are presented.
Highlights
Two-component signaling circuits (TCSs) are a ubiquitous mechanism by which bacteria sense, respond and adapt to external stimuli
It is important to note that, as predicted, overmethylation of the aspartate chemoreceptor (Tar) was observed for the minus-series (WY-3 to WY-1) of receptors, while undermethylation was seen for the plus-series (WY + 1 to WY + 3) of aromatically tuned variants [26]. These results demonstrate that signal output from Tar is modulated in an incremental manner when the aromatic residues were moved at the cytoplasmic end of Second transmembrane helix (TM2)
Aromatic tuning is advantageous compared to deletion of entire sensor histidine kinase (SHK) [60] or substitution of the conserved His residue involved in autophosphorylation and phosphotransfer because these methods may result in complete loss of kinase or phosphatase activity, which has been shown to result in non-physiological cross-talk between various two-component signaling pathways within a cell [61, 62]
Summary
Two-component signaling circuits (TCSs) are a ubiquitous mechanism by which bacteria sense, respond and adapt to external stimuli. It was shown that the contribution of interfacial anchoring, i.e., interactions between Trp residues flanking the aliphatic core and the polar/hydrophobic interfaces near the boundaries of a lipid bilayer, can dominate over the effects introduced by hydrophobic mismatch alone [16] This was only explicitly demonstrated for Trp residues, it was proposed that Tyr residues would facilitate interfacial anchoring due to possessing similar physiochemical properties [16]. When the distance between the aromatic residues was larger than the thickness of the hydrophobic core, the acyl chains within the bilayer became more ordered as determined by 2H NMR, demonstrating that the membrane is slightly expanding to accommodate these “longer” peptides [15, 17] In essence, these experiments demonstrate that amphipathic aromatic residues, namely Trp and Tyr, possess affinity for the interfacial regions where the polar phospholipid headgroups attach to the hydrophobic acyl chains.
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