2xyt: Difference between revisions
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==Crystal structure of Aplysia californica AChBP in complex with d- tubocurarine== | ==Crystal structure of Aplysia californica AChBP in complex with d- tubocurarine== | ||
<StructureSection load='2xyt' size='340' side='right' caption='[[2xyt]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='2xyt' size='340' side='right'caption='[[2xyt]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xyt]] is a 10 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2xyt]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XYT FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TC9:D-TUBOCURARINE'>TC9</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xyt OCA], [https://pdbe.org/2xyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xyt RCSB], [https://www.ebi.ac.uk/pdbsum/2xyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xyt ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 2xyt" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2xyt" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Aplysia californica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Brams M]] | ||
[[Category: Krijnen | [[Category: Krijnen L]] | ||
[[Category: Kuzmin | [[Category: Kuzmin D]] | ||
[[Category: Pandya | [[Category: Pandya A]] | ||
[[Category: Smit | [[Category: Smit AB]] | ||
[[Category: Tsetlin | [[Category: Tsetlin V]] | ||
[[Category: Ulens | [[Category: Ulens C]] | ||
[[Category: Yakel | [[Category: Yakel JL]] | ||
[[Category: | [[Category: Van Elk R]] | ||
Latest revision as of 13:41, 20 December 2023
Crystal structure of Aplysia californica AChBP in complex with d- tubocurarineCrystal structure of Aplysia californica AChBP in complex with d- tubocurarine
Structural highlights
FunctionPublication Abstract from PubMedCys-loop receptors (CLR) are pentameric ligand-gated ion channels that mediate fast excitatory or inhibitory transmission in the nervous system. Strychnine and d-tubocurarine (d-TC) are neurotoxins that have been highly instrumental in decades of research on glycine receptors (GlyR) and nicotinic acetylcholine receptors (nAChR), respectively. In this study we addressed the question how the molecular recognition of strychnine and d-TC occurs with high affinity and yet low specificity towards diverse CLR family members. X-ray crystal structures of the complexes with AChBP, a well-described structural homolog of the extracellular domain of the nAChRs, revealed that strychnine and d-TC adopt multiple occupancies and different ligand orientations, stabilizing the homopentameric protein in an asymmetric state. This introduces a new level of structural diversity in CLRs. Unlike protein and peptide neurotoxins, strychnine and d-TC form a limited number of contacts in the binding pocket of AChBP, offering an explanation for their low selectivity. Based on the ligand interactions observed in strychnine- and d-TC-AChBP complexes we performed alanine-scanning mutagenesis in the binding pocket of the human alpha1 GlyR and alpha7 nAChR and showed the functional relevance of these residues in conferring high potency of strychnine and d-TC, respectively. Our results demonstrate that a limited number of ligand interactions in the binding pocket together with an energetic stabilization of the extracellular domain are key to the poor selective recognition of strychnine and d-TC by CLRs as diverse as the GlyR, nAChR, and 5-HT(3)R. A Structural and Mutagenic Blueprint for Molecular Recognition of Strychnine and d-Tubocurarine by Different Cys-Loop Receptors.,Brams M, Pandya A, Kuzmin D, van Elk R, Krijnen L, Yakel JL, Tsetlin V, Smit AB, Ulens C PLoS Biol. 2011 Mar;9(3):e1001034. Epub 2011 Mar 29. PMID:21468359[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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