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4uxu

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Crystal Structure of the Extracellular Domain of the Human Alpha9 Nicotinic Acetylcholine Receptor In Complex with Methyllycaconitine

Structural highlights

4uxu is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.71Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACHA9_HUMAN Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion.^[1] ^[2]

Publication Abstract from PubMed

We determined the X-ray crystal structures of the extracellular domain (ECD) of the monomeric state of human neuronal alpha9 nicotinic acetylcholine receptor (nAChR) and of its complexes with the antagonists methyllycaconitine and alpha-bungarotoxin at resolutions of 1.8 A, 1.7 A and 2.7 A, respectively. The structure of the monomeric alpha9 ECD superimposed well with the structures of homologous proteins in pentameric assemblies, denoting native folding, despite the absence of a complementary subunit and transmembrane domain. The interaction motifs of both antagonists were similar to those in the complexes with homologous pentameric proteins, thus highlighting the major contribution of the principal side of alpha9 ECD to their binding. The structures revealed a functionally important beta7-beta10 strand interaction in alpha9-containing nAChRs, involving their unique Thr147, a hydration pocket similar to that of mouse alpha1 ECD and a membrane-facing network coordinated by the invariant Arg210.

Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain.,Zouridakis M, Giastas P, Zarkadas E, Chroni-Tzartou D, Bregestovski P, Tzartos SJ Nat Struct Mol Biol. 2014 Oct 5. doi: 10.1038/nsmb.2900. PMID:25282151^[3]

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

References

↑ Sgard F, Charpantier E, Bertrand S, Walker N, Caput D, Graham D, Bertrand D, Besnard F. A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Mol Pharmacol. 2002 Jan;61(1):150-9. PMID:11752216
↑ Nguyen VT, Ndoye A, Grando SA. Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity. Am J Pathol. 2000 Oct;157(4):1377-91. PMID:11021840
↑ Zouridakis M, Giastas P, Zarkadas E, Chroni-Tzartou D, Bregestovski P, Tzartos SJ. Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain. Nat Struct Mol Biol. 2014 Oct 5. doi: 10.1038/nsmb.2900. PMID:25282151 doi:http://dx.doi.org/10.1038/nsmb.2900

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4uxu"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4uxu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UXU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MLK:METHYLLYCACONITINE'>MLK</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.71&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MLK:METHYLLYCACONITINE'>MLK</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=4uxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxu OCA], [https://pdbe.org/4uxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uxu RCSB], [https://www.ebi.ac.uk/pdbsum/4uxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uxu ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 21: @@
 ==See Also==
-*[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptor]]
+*[[Acetyl choline receptor 3D structures|Acetyl choline receptor 3D structures]]
 == References ==
 <references/>

4uxu

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Current revision

Crystal Structure of the Extracellular Domain of the Human Alpha9 Nicotinic Acetylcholine Receptor In Complex with Methyllycaconitine

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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