K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac
| Autor: | Conor McClenaghan, Alexandra Mackenzie, Y.Y. Dong, N.A. Burgess-Brown, A. Quigley, Gian Filippo Ruda, Lishuang Cao, Michael V. Clausen, L. Dong, Prafulla Aryal, S. Goubin, Stephen J. Tucker, Shubhashish M.M. Mukhopadhyay, Mark S.P. Sansom, Elisabeth P. Carpenter, Mariana Grieben, Ashley C. W. Pike, Paul Brennan |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation Stereochemistry Serotonin reuptake inhibitor Molecular Sequence Data Gating Molecular Dynamics Simulation Crystallography X-Ray Protein Structure Secondary Article 03 medical and health sciences Potassium Channels Tandem Pore Domain 0302 clinical medicine Protein structure Fluoxetine medicine Humans Amino Acid Sequence Binding site 030304 developmental biology K2p channel 0303 health sciences Arachidonic Acid Binding Sites Multidisciplinary Chemistry Protein Structure Tertiary 3. Good health Transport protein Potassium Biophysics Protein folding human activities Ion Channel Gating 030217 neurology & neurosurgery medicine.drug |
| DOI: | 10.1126/science.1261512 |
| Popis: | A sensitive regulator of cellular potassium A class of potassium channels called K2P channels modulates resting membrane potential in most cells. The channels are regulated by multiple ligands, including the antidepressant drug Prozac, as well as factors such as mechanical stretch and voltage. Dong et al. determined the structure of the human K2P channel, TREK-2, in two conformations and bound to a metabolite of Prozac. The structures show how ligand binding or mechanical stretch might induce switching between the states. Although both states have open channels, one appears primed for gating. A Prozac metabolite binds to the primed state and prevents conformational switching. K2P channels are not a target of Prozac, but their inhibition may contribute to side effects. Science , this issue p. 1256 |
| Databáze: | OpenAIRE |
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