Tuning Chemoreceptor Signaling by Positioning Aromatic Residues at the Lipid–Aqueous Interface

Abstract

Aromatic tuning facilitates stimulus-independent modulation of receptor output. The methodology is based upon the affinity of amphipathic aromatic residues, namely Trp and Tyr, for the polar-hydrophobic interfaces found within biological membranes. Here, we describe the application of aromatic tuning within the aspartate chemoreceptor of Escherichia coli (Tar). We have also employed the method within other related proteins, such as sensor histidine kinases (SHKs), and therefore hope that other research groups find it useful to modulate signal output from their receptor of interest.

Allosteric mechanism of signal transduction in the two-component system histidine kinase PhoQ

“…Ala and Phe substitutions were evaluated at sites expected to be on the interior of the protein; these mutants were expected to alter the relative energetics of the kinase- versus phosphatase-promoting states by altering core packing geometry ( Airola et al, 2013 ; Ferris et al, 2011 ; Hulko et al, 2006 ; Bi et al, 2018 ). We also examined the effects of Trp substitutions in the TM helix at positions expected to map to the headgroup region of the bilayer, as similar substitutions often induce changes in signaling ( Draheim et al, 2005 ; Lehning et al, 2017 ; Inda et al, 2016 ; Monzel and Unden, 2015 ; Yusuf and Draheim, 2015 ; Yusuf et al, 2018 ; Adase et al, 2013 ). We also included several mutations, particularly in the C-terminal half of the HAMP domain, that show altered autokinase activity as compared to WT PhoQ.…”