View source for 6pv8


==Human alpha3beta4 nicotinic acetylcholine receptor in complex with AT-1001==
<StructureSection load='6pv8' size='340' side='right'caption='[[6pv8]], [[Resolution|resolution]] 3.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pv8]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PV8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P1M:(3-endo)-N-(2-bromophenyl)-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine'>P1M</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHRNA3, NACHRA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CHRNB4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6pv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pv8 OCA], [http://pdbe.org/6pv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pv8 RCSB], [http://www.ebi.ac.uk/pdbsum/6pv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pv8 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/ACHB4_HUMAN ACHB4_HUMAN]] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. [[http://www.uniprot.org/uniprot/ACHA3_HUMAN ACHA3_HUMAN]] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. 
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== Publication Abstract from PubMed ==
Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The alpha3beta4 nicotinic receptor subtype forms the principal relay between the central and peripheral nervous systems in the autonomic ganglia. This receptor is also expressed focally in brain areas that affect reward circuits and addiction. Here, we present structures of the alpha3beta4 nicotinic receptor in lipidic and detergent environments, using functional reconstitution to define lipids appropriate for structural analysis. The structures of the receptor in complex with nicotine, as well as the alpha3beta4-selective ligand AT-1001, complemented by molecular dynamics, suggest principles of agonist selectivity. The structures further reveal much of the architecture of the intracellular domain, where mutagenesis experiments and simulations define residues governing ion conductance.

Agonist Selectivity and Ion Permeation in the alpha3beta4 Ganglionic Nicotinic Receptor.,Gharpure A, Teng J, Zhuang Y, Noviello CM, Walsh RM Jr, Cabuco R, Howard RJ, Zaveri NT, Lindahl E, Hibbs RE Neuron. 2019 Nov 6;104(3):501-511.e6. doi: 10.1016/j.neuron.2019.07.030. Epub, 2019 Sep 2. PMID:31488329<ref>PMID:31488329</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pv8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cabuco, R]]
[[Category: Gharpure, A]]
[[Category: Hibbs, R E]]
[[Category: Howard, R J]]
[[Category: Lindahl, E]]
[[Category: Noviello, C M]]
[[Category: Teng, J]]
[[Category: Walsh, R M]]
[[Category: Zaveri, N T]]
[[Category: Zhuang, Y]]
[[Category: Cys-loop receptor]]
[[Category: Ligand-gated ion channel]]
[[Category: Membrane protein]]
[[Category: Nicotinic acetylcholine receptor]]