Concerted Differential Changes of Helical Dynamics and Packing upon Ligand Occupancy in a Bacterial Chemoreceptor

Transmembrane receptors are central components of the chemosensory systems by which motile bacteria detect and respond to chemical gradients. An attractant bound to the receptor periplasmic domain generates conformational signals that regulate a histidine kinase interacting with its cytoplasmic doma...

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Veröffentlicht in:ACS chemical biology 2021-11, Vol.16 (11), p.2472-2480
Hauptverfasser: Gordon, Jesse B, Hoffman, Mikaila C, Troiano, Julianne M, Li, Mingshan, Hazelbauer, Gerald L, Schlau-Cohen, Gabriela S
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container_end_page 2480
container_issue 11
container_start_page 2472
container_title ACS chemical biology
container_volume 16
creator Gordon, Jesse B
Hoffman, Mikaila C
Troiano, Julianne M
Li, Mingshan
Hazelbauer, Gerald L
Schlau-Cohen, Gabriela S
description Transmembrane receptors are central components of the chemosensory systems by which motile bacteria detect and respond to chemical gradients. An attractant bound to the receptor periplasmic domain generates conformational signals that regulate a histidine kinase interacting with its cytoplasmic domain. Ligand-induced signaling through the periplasmic and transmembrane domains of the receptor involves a piston-like helical displacement, but the nature of this signaling through the >200 Å four-helix coiled coil of the cytoplasmic domain had not yet been identified. We performed single-molecule Förster resonance energy transfer measurements on Escherichia coli aspartate receptor homodimers inserted into native phospholipid bilayers enclosed in nanodiscs. The receptors were labeled with fluorophores at diagnostic positions near the middle of the cytoplasmic coiled coil. At these positions, we found that the two N-helices of the homodimer were more distant, that is, less tightly packed and more dynamic than the companion C-helix pair, consistent with previous deductions that the C-helices form a stable scaffold and the N-helices are dynamic. Upon ligand binding, the scaffold pair compacted further, while separation and dynamics of the dynamic pair increased. Thus, ligand binding had asymmetric effects on the two helical pairs, shifting mean distances in opposite directions and increasing the dynamics of one pair. We suggest that this reflects a conformational change in which differential alterations to the packing and dynamics of the two helical pairs are coupled. These coupled changes could represent a previously unappreciated mode of conformational signaling that may well occur in other coiled-coil signaling proteins.
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Biol</addtitle><date>2021-11-19</date><risdate>2021</risdate><volume>16</volume><issue>11</issue><spage>2472</spage><epage>2480</epage><pages>2472-2480</pages><issn>1554-8929</issn><eissn>1554-8937</eissn><abstract>Transmembrane receptors are central components of the chemosensory systems by which motile bacteria detect and respond to chemical gradients. An attractant bound to the receptor periplasmic domain generates conformational signals that regulate a histidine kinase interacting with its cytoplasmic domain. Ligand-induced signaling through the periplasmic and transmembrane domains of the receptor involves a piston-like helical displacement, but the nature of this signaling through the &gt;200 Å four-helix coiled coil of the cytoplasmic domain had not yet been identified. We performed single-molecule Förster resonance energy transfer measurements on Escherichia coli aspartate receptor homodimers inserted into native phospholipid bilayers enclosed in nanodiscs. 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subjects Bacterial Proteins - metabolism
Escherichia coli - metabolism
Fluorescence Resonance Energy Transfer
Ligands
Protein Conformation
Signal Transduction
title Concerted Differential Changes of Helical Dynamics and Packing upon Ligand Occupancy in a Bacterial Chemoreceptor
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