You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Bacterial chemoreceptors lock down CheA
In bacteria, lattice-like arrays of transmembrane chemoreceptors and their downstream intracellular mediators couple the detection of external chemical cues to directional switching of the flagellar motor. Signaling through this system depends on the activity of the histidine kinase CheA, which interacts with the receptors through the adaptor protein CheW. In natural arrays, receptor trimers contribute to the receptor-CheW-CheA core signaling units. Muok et al. engineered and purified trimeric single-chain receptor polypeptides that formed functional signaling units with CheW and CheA in the kinase-off state. The model developed through extensive structural and biochemical analyses of these reconstituted core units revealed that chemoreceptors maintained the inhibited state of the signaling core by preventing the domains of CheA that form the active kinase from interacting productively.
Abstract
Bacterial chemoreceptors, the histidine kinase CheA, and the coupling protein CheW form transmembrane molecular arrays with remarkable sensing properties. The receptors inhibit or stimulate CheA kinase activity depending on the presence of attractants or repellants, respectively. We engineered chemoreceptor cytoplasmic regions to assume a trimer of receptor dimers configuration that formed well-defined complexes with CheA and CheW and promoted a CheA kinase-off state. These mimics of core signaling units were assembled to homogeneity and investigated by site-directed spin-labeling with pulse-dipolar electron-spin resonance spectroscopy (PDS), small-angle x-ray scattering, targeted protein cross-linking, and cryo–electron microscopy. The kinase-off state was especially stable, had relatively low domain mobility, and associated the histidine substrate and docking domains with the kinase core, thus preventing catalytic activity. Together, these data provide an experimentally restrained model for the inhibited state of the core signaling unit and suggest that chemoreceptors indirectly sequester the kinase and substrate domains to limit histidine autophosphorylation.
This is an article distributed under the terms of the Science Journals Default License.
