Structural features and signalling mechanisms of transmembrane chemoreceptors identified utilizing Nanodiscs

Transmembrane chemoreceptors are central components in the sensory system that mediates bacterial chemotaxis. Like many transmembrane proteins, these receptors are fully active only if inserted in a lipid bilayer. This requirement presents a challenge for in vitro analysis by many biochemical and structural techniques. The challenge is met by Nanodiscs, soluble, nanoscale (~10 nm diameter) particles of lipid bilayer surrounded by an annulus of amphipathic protein into which transmembrane proteins can be incorporated. Using Nanodiscs, we documented that chemoreceptor dimers bend at a specific locus along their 300 Å long axis, discovered that conformational differences between chemoreceptor signalling states were differential propensities of receptor helices to become momentarily unstructured, and determined that chemoreceptor signalling complexes activate and control the chemotaxis histidine kinase by altering its catalytic rate constant.