Multi-Site Binding Of A General Anesthetic To The Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC
نویسندگان
چکیده
1 From the Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, KULeuven, Herestraat 49, PB 601, B-3000 Leuven, Belgium 2 Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 1 University Station A4800, Austin, TX 78712, U.S.A. 3 Department of Biochemistry, University of Cambridge, University of Cambridge, Tennis Court Road, Cambridge CB 1QW, United Kingdom 4 Laboratory of Biocrystallography, KULeuven, Herestraat 49, PB 822, B-3000 Leuven, Belgium 5 Laboratory of Toxicology, KULeuven, Herestraat 49, PB 922, B-3000 Leuven, Belgium 6 HiQScreen Sàrl, 15 rue de l’Athénée, Case Postale 209, CH-1211 Geneva 12, Switzerland
منابع مشابه
Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.
BACKGROUND Identifying functionally relevant anesthetic-binding sites in pentameric ligand-gated ion channels (pLGICs) is an important step toward understanding the molecular mechanisms underlying anesthetic action. The anesthetic propofol is known to inhibit cation-conducting pLGICs, including a prokaryotic pLGIC from Erwinia chrysanthemi (ELIC), but the sites responsible for functional inhibi...
متن کاملDirect Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC
Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane oc...
متن کاملInhibition of the Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC by Divalent Cations
The modulation of pentameric ligand-gated ion channels (pLGICs) by divalent cations is believed to play an important role in their regulation in a physiological context. Ions such as calcium or zinc influence the activity of pLGIC neurotransmitter receptors by binding to their extracellular domain and either potentiate or inhibit channel activation. Here we have investigated by electrophysiolog...
متن کاملPentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.
GABA(A) receptors are pentameric ligand-gated ion channels involved in fast inhibitory neurotransmission and are allosterically modulated by the anxiolytic, anticonvulsant, and sedative-hypnotic benzodiazepines. Here we show that the prokaryotic homolog ELIC also is activated by GABA and is modulated by benzodiazepines with effects comparable to those at GABA(A) receptors. Crystal structures re...
متن کاملLigand Activation of the Prokaryotic Pentameric Ligand-Gated Ion Channel ELIC
While the pentameric ligand-gated ion channel ELIC has recently provided first insight into the architecture of the family at high resolution, its detailed investigation was so far prevented by the fact that activating ligands were unknown. Here we describe a study on the functional characterization of ELIC by electrophysiology and X-ray crystallography. ELIC is activated by a class of primary ...
متن کاملStructure of the pentameric ligand-gated ion channel GLIC bound with anesthetic ketamine.
Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but a structural understanding of anesthetic action on pLGICs remains elusive. GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine. The ketamine concentration leading to half-maximal inhibition of GLIC (58 μM) is comparable to that on neuronal nicotinic acetylcholine receptors. A 2.99 Å ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2013