Miller, P.S. and Topf, Maya and Smart, T.G. (2008) Mapping a molecular link between allosteric inhibition and activation of the glycine receptor. Nature Structural & Molecular Biology 15 , pp. 1084-1093. ISSN 1545-9985.
Abstract
Cys-loop ligand-gated ion channels mediate rapid neurotransmission throughout the central nervous system. They possess agonist recognition sites and allosteric sites where modulators regulate ion channel function. Using strychnine-sensitive glycine receptors, we identified a scaffold of hydrophobic residues enabling allosteric communication between glycine-agonist binding loops A and D, and the Zn2+-inhibition site. Mutating these hydrophobic residues disrupted Zn2+ inhibition, generating novel Zn2+-activated receptors and spontaneous channel activity. Homology modeling and electrophysiology revealed that these phenomena are caused by disruption to three residues on the '-' loop face of the Zn2+-inhibition site, and to D84 and D86, on a neighboring beta3 strand, forming a Zn2+-activation site. We provide a new view for the activation of a Cys-loop receptor where, following agonist binding, the hydrophobic core and interfacial loops reorganize in a concerted fashion to induce downstream gating.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 04 Aug 2010 14:09 |
| Last Modified: | 02 Aug 2023 16:49 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/1143 |
Statistics
Additional statistics are available via IRStats2.
Archive Staff Only (login required)
