Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall
- PMID: 10329178
- DOI: 10.1006/jmbi.1999.2721
Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall
Abstract
The nicotinic acetylcholine (ACh) receptor is the neurotransmitter-gated ion channel responsible for the rapid propagation of electrical signals between cells at the nerve/muscle synapse. We report here the 4.6 A structure of this channel in the closed conformation, determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes embedded in amorphous ice. The analysis was conducted on images recorded at 4 K with a 300 kV field emission source, by combining data from four helical families of tubes (-16,6; -18,6; -15,7; -17,5), and applying three-dimensional corrections for lattice distortions. The study extends earlier work on the same specimen at 9 A resolution. Several features having functional implications now appear with better definition. The gate of the channel forms a narrow bridge, consisting of no more than one or two rings of side-chains, across the middle portion of the membrane-spanning pore. Tunnels, framed by twisted beta-sheet strands, are resolved in the extracellular wall of the channel connecting the water-filled vestibule to the putative ACh-binding pockets. A set of narrow openings through which ions can flow are resolved between alpha-helical segments forming part of the cytoplasmic wall of the channel. It is suggested that the extracellular tunnels are access routes to the binding pockets for ACh, and that the cytoplasmic openings serve as filters to exclude anions and other impermeant species from the vicinity of the pore. Both transverse pathways are likely to be important in achieving a rapid postsynaptic response.
Copyright 1999 Academic Press.
Similar articles
-
The nicotinic acetylcholine receptor of the Torpedo electric ray.J Struct Biol. 1998;121(2):181-90. doi: 10.1006/jsbi.1997.3949. J Struct Biol. 1998. PMID: 9615437 Review.
-
Nicotinic acetylcholine receptor at 9 A resolution.J Mol Biol. 1993 Feb 20;229(4):1101-24. doi: 10.1006/jmbi.1993.1107. J Mol Biol. 1993. PMID: 8445638
-
Structure and action of the nicotinic acetylcholine receptor explored by electron microscopy.FEBS Lett. 2003 Nov 27;555(1):91-5. doi: 10.1016/s0014-5793(03)01084-6. FEBS Lett. 2003. PMID: 14630325 Review.
-
Nicotinic acetylcholine receptor and the structural basis of neuromuscular transmission: insights from Torpedo postsynaptic membranes.Q Rev Biophys. 2013 Nov;46(4):283-322. doi: 10.1017/S0033583513000061. Epub 2013 Sep 20. Q Rev Biophys. 2013. PMID: 24050525 Free PMC article. Review.
-
Projection structure of the nicotinic acetylcholine receptor: distinct conformations of the alpha subunits.J Mol Biol. 1996 Apr 5;257(3):586-96. doi: 10.1006/jmbi.1996.0187. J Mol Biol. 1996. PMID: 8648626
Cited by
-
Gating movement of acetylcholine receptor caught by plunge-freezing.J Mol Biol. 2012 Oct 5;422(5):617-634. doi: 10.1016/j.jmb.2012.07.010. Epub 2012 Jul 24. J Mol Biol. 2012. PMID: 22841691 Free PMC article.
-
Cellular membrane phospholipids act as a depository for quaternary amine containing drugs thus competing with the acetylcholine/nicotinic receptor.J Proteome Res. 2012 Jun 1;11(6):3382-9. doi: 10.1021/pr300184g. Epub 2012 Apr 30. J Proteome Res. 2012. PMID: 22506649 Free PMC article.
-
An Inside Job: Molecular Determinants for Postsynaptic Localization of Nicotinic Acetylcholine Receptors.Molecules. 2021 May 21;26(11):3065. doi: 10.3390/molecules26113065. Molecules. 2021. PMID: 34063759 Free PMC article. Review.
-
Looking below the surface of nicotinic acetylcholine receptors.Trends Pharmacol Sci. 2015 Aug;36(8):514-23. doi: 10.1016/j.tips.2015.05.002. Epub 2015 Jun 8. Trends Pharmacol Sci. 2015. PMID: 26067101 Free PMC article. Review.
-
Gating reaction mechanisms for NMDA receptor channels.J Neurosci. 2005 Aug 31;25(35):7914-23. doi: 10.1523/JNEUROSCI.1471-05.2005. J Neurosci. 2005. PMID: 16135748 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources