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'''Unreleased structure'''


The entry 9qto is ON HOLD  until Paper Publication
==Human alpha7 nicotinic receptor in complex with the E6 nanobody==
<StructureSection load='9qto' size='340' side='right'caption='[[9qto]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qto]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QTO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QTO 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]] 2.16&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=9qto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qto OCA], [https://pdbe.org/9qto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qto RCSB], [https://www.ebi.ac.uk/pdbsum/9qto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qto ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
alpha7 nicotinic receptors are neurotransmitter-gated ion channels involved in neurological and inflammatory diseases. Ligands acting on its neurotransmitter binding site and on the channel domain of alpha7 have been extensively developed, yielding a wide range of orthosteric effectors and allosteric positive modulators. Here, we present the functional and structural characterization of two camelid antibody fragments, or nanobodies, F1 and E6, that inhibit alpha7 activity by acting as negative allosteric modulators, an underrepresented class of ligands. Cryo-EM structures of the nanobodies in complex with alpha7 show that both nanobodies form a pentameric bundle at the apex of the receptor, each nanobody interacting through a conserved set of residues at alpha7 subunit interfaces. Electrophysiological experiments suggest that E6 inhibits the activity of alpha7 by stabilizing its resting conformation, and that internanobodies interactions are key to its activity. Those two nanobodies expand the toolbox for human alpha7 modulation, opening new possibilities for its pharmacological control with far reaching potentialities in clinics.


Authors: Barilone, N., Vangelatou, M., Marouf, F.Z., Dejean de la Batie, G., Ayme, G., Lafaye, P., Corringer, P.-J., Prevost, M.S.
Discovery and mechanism of negative allosteric modulation of the alpha7 nicotinic acetylcholine receptor by nanobodies.,Barilone N, Vangelatou M, Marouf FZ, Dejean de la Batie G, Li Q, Lafaye P, Ayme G, Corringer PJ, Prevost MS Proc Natl Acad Sci U S A. 2026 Jan 27;123(4):e2514734123. doi: , 10.1073/pnas.2514734123. Epub 2026 Jan 23. PMID:41576092<ref>PMID:41576092</ref>


Description: Human alpha7 nicotinic receptor in complex with the E6 nanobody
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Dejean De La Batie, G]]
<div class="pdbe-citations 9qto" style="background-color:#fffaf0;"></div>
[[Category: Prevost, M.S]]
== References ==
[[Category: Ayme, G]]
<references/>
[[Category: Barilone, N]]
__TOC__
[[Category: Corringer, P.-J]]
</StructureSection>
[[Category: Marouf, F.Z]]
[[Category: Homo sapiens]]
[[Category: Lafaye, P]]
[[Category: Large Structures]]
[[Category: Vangelatou, M]]
[[Category: Vicugna pacos]]
[[Category: Ayme G]]
[[Category: Barilone N]]
[[Category: Corringer P-J]]
[[Category: Dejean de la Batie G]]
[[Category: Lafaye P]]
[[Category: Marouf FZ]]
[[Category: Prevost MS]]
[[Category: Vangelatou M]]
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