View source for 8byi


==Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in complex with CHAPS(Alpo4_CHAPS)==
<StructureSection load='8byi' size='340' side='right'caption='[[8byi]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8byi]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Alvinella_pompejana Alvinella pompejana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BYI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8byi OCA], [https://pdbe.org/8byi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8byi RCSB], [https://www.ebi.ac.uk/pdbsum/8byi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8byi ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cys-loop receptors or pentameric ligand-gated ion channels are mediators of electrochemical signaling throughout the animal kingdom. Because of their critical function in neurotransmission and high potential as drug targets, Cys-loop receptors from humans and closely related organisms have been thoroughly investigated, whereas molecular mechanisms of neurotransmission in invertebrates are less understood. When compared with vertebrates, the invertebrate genomes underwent a drastic expansion in the number of the nACh-like genes associated with receptors of unknown function. Understanding this diversity contributes to better insight into the evolution and possible functional divergence of these receptors. In this work, we studied orphan receptor Alpo4 from an extreme thermophile worm Alvinella pompejana. Sequence analysis points towards its remote relation to characterized nACh receptors. We solved the cryo-EM structure of the lophotrochozoan nACh-like receptor in which a CHAPS molecule is tightly bound to the orthosteric site. We show that the binding of CHAPS leads to extending of the loop C at the orthosteric site and a quaternary twist between extracellular and transmembrane domains. Both the ligand binding site and the channel pore reveal unique features. These include a conserved Trp residue in loop B of the ligand binding site which is flipped into an apparent self-liganded state in the apo structure. The ion pore of Alpo4 is tightly constricted by a ring of methionines near the extracellular entryway of the channel pore. Our data provide a structural basis for a functional understanding of Alpo4 and hints towards new strategies for designing specific channel modulators.

Sterol derivative binding to the orthosteric site causes conformational changes in an invertebrate Cys-loop receptor.,De Gieter S, Gallagher CI, Wijckmans E, Pasini D, Ulens C, Efremov RG Elife. 2023 Jul 3;12:e86029. doi: 10.7554/eLife.86029. PMID:37395731<ref>PMID:37395731</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8byi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetyl choline receptor 3D structures|Acetyl choline receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Alvinella pompejana]]
[[Category: Large Structures]]
[[Category: De Gieter S]]
[[Category: Efremov RG]]
[[Category: Ulens C]]