期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 45, 页码 15940-15945出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1415184111
关键词
transmembrane receptors; bacterial chemotaxis; allosteric coupling; histidine kinases; Nanodiscs
资金
- National Institute of General Medical Sciences [GM29963]
Bacterial chemotaxis is mediated by signaling complexes that sense chemical gradients and direct bacteria to favorable environments by controlling a histidine kinase as a function of chemoreceptor ligand occupancy. Core signaling complexes contain two trimers of transmembrane chemoreceptor dimers, each trimer binding a coupling protein CheW and a protomer of the kinase dimer. Core complexes assemble into hexagons, and these form hexagonal arrays. The notable cooperativity and amplification in bacterial chemotaxis is thought to reflect allosteric interactions in cores, hexagons, and arrays, but little is known about this presumed allostery. We investigated allostery in core complexes assembled with two chemoreceptor species, each recognizing a different ligand. Chemoreceptors were inserted in Nanodiscs, which rendered them water soluble and allowed isolation of individual complexes. Neighboring dimers in receptor trimers influenced one another's operational ligand affinity, indicating allosteric coupling. However, this coupling did not include the key function of kinase inhibition. Our data indicated that only one receptor dimer could inhibit kinase as a function of ligand occupancy. This selective allosteric coupling corresponded with previously identified structural asymmetry: only one dimer in a trimer contacts kinase and only one CheW. We suggest one of these dimers couples ligand occupancy to kinase inhibition. Additionally, we found that kinase protomers are allosterically coupled, conveying inhibition across the dimer interface. Because kinase dimers connect core complex hexagons, allosteric communication across dimer interfaces provides a pathway for receptor-generated kinase inhibition in one hexagon to spread to another, providing a crucial step for the extensive amplification characteristic of chemotactic signaling.
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