We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

5mvn

From Proteopedia

Jump to: navigation, search

X-ray structure of the M205W mutant of GLIC in complex with propofol

Structural highlights

5mvn is a 5 chain structure with sequence from Gloeobacter violaceus PCC 7421. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.49Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLIC_GLOVI Cationic channel with similar permeabilities for Na(+) and K(+), that is activated by an increase of the proton concentration on the extracellular side. Displays no permeability for chloride ions. Shows slow kinetics of activation, no desensitization and a single channel conductance of 8 pS. Might contribute to adaptation to external pH change.^[1]

Publication Abstract from PubMed

Ion channel modulation by general anesthetics is a vital pharmacological process with implications for receptor biophysics and drug development. Functional studies have implicated conserved sites of both potentiation and inhibition in pentameric ligand-gated ion channels, but a detailed structural mechanism for these bimodal effects is lacking. The prokaryotic model protein GLIC recapitulates anesthetic modulation of human ion channels, and it is accessible to structure determination in both apparent open and closed states. Here, we report ten X-ray structures and electrophysiological characterization of GLIC variants in the presence and absence of general anesthetics, including the surgical agent propofol. We show that general anesthetics can allosterically favor closed channels by binding in the pore or favor open channels via various subsites in the transmembrane domain. Our results support an integrated, multi-site mechanism for allosteric modulation, and they provide atomic details of both potentiation and inhibition by one of the most common general anesthetics.

Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels.,Fourati Z, Howard RJ, Heusser SA, Hu H, Ruza RR, Sauguet L, Lindahl E, Delarue M Cell Rep. 2018 Apr 24;23(4):993-1004. doi: 10.1016/j.celrep.2018.03.108. PMID:29694907^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, Taly A, Grutter T, Changeux JP, Corringer PJ. A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature. 2007 Jan 4;445(7123):116-9. Epub 2006 Dec 10. PMID:17167423 doi:10.1038/nature05371
↑ Fourati Z, Howard RJ, Heusser SA, Hu H, Ruza RR, Sauguet L, Lindahl E, Delarue M. Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels. Cell Rep. 2018 Apr 24;23(4):993-1004. doi: 10.1016/j.celrep.2018.03.108. PMID:29694907 doi:http://dx.doi.org/10.1016/j.celrep.2018.03.108