Concerted Differential Changes of Helical Dynamics and Packing upon Ligand Occupancy in a Bacterial Chemoreceptor
| Autor: | Gabriela S. Schlau-Cohen, Mikaila C Hoffman, Julianne M Troiano, Jesse B. Gordon, Mingshan Li, Gerald L. Hazelbauer |
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| Rok vydání: | 2021 |
| Předmět: |
Coiled coil
0303 health sciences Conformational change Protein Conformation Chemistry 030302 biochemistry & molecular biology Histidine kinase General Medicine Periplasmic space Ligands Ligand (biochemistry) Biochemistry Article 03 medical and health sciences Transmembrane domain Förster resonance energy transfer Bacterial Proteins Cell surface receptor Escherichia coli Fluorescence Resonance Energy Transfer Biophysics Molecular Medicine Signal Transduction 030304 developmental biology |
| Zdroj: | ACS Chem Biol |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.1c00576 |
| Popis: | 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 A four-helix coiled coil of the cytoplasmic domain had not yet been identified. We performed single-molecule Forster 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. |
| Databáze: | OpenAIRE |
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