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| | <StructureSection load='3wip' size='340' side='right'caption='[[3wip]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='3wip' size='340' side='right'caption='[[3wip]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wip]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Great_pond_snail Great pond snail]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WIP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WIP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wip]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WIP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACH:ACETYLCHOLINE'>ACH</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</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=3wip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wip OCA], [http://pdbe.org/3wip PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wip RCSB], [http://www.ebi.ac.uk/pdbsum/3wip PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wip ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACH:ACETYLCHOLINE'>ACH</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3wip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wip OCA], [https://pdbe.org/3wip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wip RCSB], [https://www.ebi.ac.uk/pdbsum/3wip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wip ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST]] Binds to acetylcholine. Modulates neuronal synaptic transmission. | + | [https://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Great pond snail]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ahring, P K]] | + | [[Category: Lymnaea stagnalis]] |
| - | [[Category: Balle, T]] | + | [[Category: Ahring PK]] |
| - | [[Category: Gajhede, M]] | + | [[Category: Balle T]] |
| - | [[Category: Kastrup, J S]] | + | [[Category: Gajhede M]] |
| - | [[Category: Olsen, J A]] | + | [[Category: Kastrup JS]] |
| - | [[Category: Acetylcholine]]
| + | [[Category: Olsen JA]] |
| - | [[Category: Acetylcholine-binding protein]]
| + | |
| - | [[Category: Acetylcholine-binding protein-agonist complex]]
| + | |
| - | [[Category: Agonist]]
| + | |
| - | [[Category: Lymnaea stagnali]]
| + | |
| Structural highlights
3wip is a 10 chain structure with sequence from Lymnaea stagnalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.6Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ACHP_LYMST Binds to acetylcholine. Modulates neuronal synaptic transmission.
Publication Abstract from PubMed
Despite extensive studies on nicotinic acetylcholine receptors (nAChRs) and homologues, details of acetylcholine binding are not completely resolved. Here, we report the crystal structure of acetylcholine bound to the receptor homologue acetylcholine binding protein from Lymnaea stagnalis. This is the first structure of acetylcholine in a binding pocket containing all five aromatic residues conserved in all mammalian nAChRs. The ligand-protein interactions are characterized by contacts to the aromatic box formed primarily by residues on the principal side of the intersubunit binding interface (residues Tyr89, Trp143 and Tyr185). Besides these interactions on the principal side, we observe a cation-pi interaction between acetylcholine and Trp53 on the complementary side and a water-mediated hydrogen bond from acetylcholine to backbone atoms of Leu102 and Met114, both of importance for anchoring acetylcholine to the complementary side. To further study the role of Trp53, we mutated the corresponding tryptophan in the two different acetylcholine-binding interfaces of the widespread alpha4beta2 nAChR, i.e. the interfaces alpha4(+)beta2(-) and alpha4(+)alpha4(-). Mutation to alanine (W82A on the beta2 subunit or W88A on the alpha4 subunit) significantly altered the response to acetylcholine measured by oocyte voltage-clamp electrophysiology in both interfaces. This shows that the conserved tryptophan residue is important for the effects of ACh at alpha4beta2 nAChRs, as also indicated by the crystal structure. The results add important details to the understanding of how this neurotransmitter exerts its action and improves the foundation for rational drug design targeting these receptors.
Molecular recognition of the neurotransmitter acetylcholine by an acetylcholine binding protein reveals determinants of binding to nicotinic acetylcholine receptors.,Olsen JA, Balle T, Gajhede M, Ahring PK, Kastrup JS PLoS One. 2014 Mar 17;9(3):e91232. doi: 10.1371/journal.pone.0091232. eCollection, 2014. PMID:24637639[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Olsen JA, Balle T, Gajhede M, Ahring PK, Kastrup JS. Molecular recognition of the neurotransmitter acetylcholine by an acetylcholine binding protein reveals determinants of binding to nicotinic acetylcholine receptors. PLoS One. 2014 Mar 17;9(3):e91232. doi: 10.1371/journal.pone.0091232. eCollection, 2014. PMID:24637639 doi:http://dx.doi.org/10.1371/journal.pone.0091232
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