View source for 2xz5


==MMTS-modified Y53C mutant of Aplysia AChBP in complex with acetylcholine==
<StructureSection load='2xz5' size='340' side='right'caption='[[2xz5]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xz5]] is a 5 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=2XZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XZ5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACH:ACETYLCHOLINE'>ACH</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</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=2xz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xz5 OCA], [https://pdbe.org/2xz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2xz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xz5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Covalent modification of alpha7 W55C nicotinic acetylcholine receptors (nAChR) with the cysteine-modifying reagent MTSET(+) produces receptors that are unresponsive to acetylcholine, whereas MMTS produces enhanced acetylcholine-gated currents. Here, we investigate structural changes that underlie these opposite effects of MTSET(+) and MMTS using acetylcholine binding protein (AChBP), a homolog of the extracellular domain of the nAChR. Crystal structures of Y53C AChBP show that MTSET(+)-modification stabilizes loop C in an extended conformation that resembles the antagonist-bound state, which parallels our observation that MTSET(+) produces unresponsive W55C nAChRs. The MMTS-modified mutant in complex with acetylcholine is characterized by a contracted C loop, similar to other agonist-bound complexes. Surprisingly, we find two acetylcholine molecules bound in the ligand-binding site, which might explain the potentiating effect of MMTS-modification in W55C nAChRs. Unexpectedly, we observed in the MMTS-Y53C structure that ten phosphate ions arranged in two rings at adjacent sites are bound in the vestibule of AChBP. We mutated homologous residues in the vestibule of alpha1 GlyR and observed a reduction in the single channel conductance, suggesting a role of this site in ion permeation. Taken together, our results demonstrate that targeted modification of a conserved aromatic residue in loop D is sufficient for a conformational switch of AChBP and that a defined region in the vestibule of the extracellular domain contributes to ion conduction in anion-selective cys-loop receptors.

Crystal structures of a cysteine-modified mutant in loop D of acetylcholine binding protein.,Brams M, Gay EA, Saez JC, Guskov A, van Elk R, van der Schors RC, Peigneur S, Tytgat J, Strelkov SV, Smit AB, Yakel JL, Ulens C J Biol Chem. 2010 Nov 29. PMID:21115477<ref>PMID:21115477</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xz5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aplysia californica]]
[[Category: Large Structures]]
[[Category: Brams M]]
[[Category: Colon Saez J]]
[[Category: Gay EA]]
[[Category: Guskov A]]
[[Category: Peigneur S]]
[[Category: Smit AB]]
[[Category: Strelkov SV]]
[[Category: Tytgat J]]
[[Category: Ulens C]]
[[Category: Yakel JL]]
[[Category: Van Elk R]]
[[Category: Van der Schors RC]]