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2jus
From Proteopedia
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| + | ==alpha RgIA, a Novel Conotoxin that Blocks the alpha9-alpha10 nAChR== | ||
| + | <StructureSection load='2jus' size='340' side='right'caption='[[2jus]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2jus]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JUS FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2juq|2juq]], [[2jur|2jur]], [[2jut|2jut]]</div></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=2jus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jus OCA], [https://pdbe.org/2jus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jus RCSB], [https://www.ebi.ac.uk/pdbsum/2jus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jus ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/CXA1A_CONRE CXA1A_CONRE]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. Is a specific blocker of the alpha-9/alpha-10 nAChR. Is also active on alpha-7 (but 1000-fold less potent) and on alpha-2/beta-2, alpha-2/beta-4, alpha-3/beta-4, alpha-3/beta-2, alpha-4/beta-2, alpha-4/beta-4 and alpha-6 or -3/beta-2 or -3 (but 2000-fold less potent) channels.<ref>PMID:16445293</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Alpha-conotoxins are small disulfide-constrained peptides from cone snails that act as antagonists at specific subtypes of nicotinic acetylcholine receptors (nAChRs). The 13-residue peptide alpha-conotoxin RgIA (alpha-RgIA) is a member of the alpha-4,3 family of alpha-conotoxins and selectively blocks the alpha9alpha10 nAChR subtype, in contrast to another well-characterized member of this family, alpha-conotoxin ImI (alpha-ImI), which is a potent inhibitor of the alpha7 and alpha3beta2 nAChR subtypes. In this study, we have altered side chains in both the four-residue and the three-residue loops of alpha-RgIA, and have modified its C-terminus. The effects of these changes on activity against alpha9alpha10 and alpha7 nAChRs were measured; the solution structures of alpha-RgIA and its Y10W, D5E, and P6V analogues were determined from NMR data; and resonance assignments were made for alpha-RgIA [R9A]. The structures for alpha-RgIA and its three analogues were well defined, except at the chain termini. Comparison of these structures with reported structures of alpha-ImI reveals a common two-loop backbone architecture within the alpha-4,3 family, but with variations in side-chain solvent accessibility and orientation. Asp5, Pro6, and Arg7 in loop 1 are critical for blockade of both the alpha9alpha10 and the alpha7 subtypes. In loop 2, alpha-RgIA [Y10W] had activity near that of wild-type alpha-RgIA, with high potency for alpha9alpha10 and low potency for alpha7, and had a structure similar to that of wild type. By contrast, Arg9 in loop 2 is critical for specific binding to the alpha9alpha10 subtype, probably because it is larger and more solvent accessible than Ala9 in alpha-ImI. Our findings contribute to a better understanding of the molecular basis for antagonism of the alpha9alpha10 nAChR subtype, which is a target for the development of analgesics for the treatment of chronic neuropathic pain. | ||
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| + | Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR: structure and identification of key receptor-binding residues.,Ellison M, Feng ZP, Park AJ, Zhang X, Olivera BM, McIntosh JM, Norton RS J Mol Biol. 2008 Apr 4;377(4):1216-27. Epub 2008 Feb 4. PMID:18295795<ref>PMID:18295795</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2jus" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ellison, M]] | ||
| + | [[Category: Feng, Z]] | ||
| + | [[Category: Disulfide bond]] | ||
| + | [[Category: Signaling protein inhibitor]] | ||
| + | [[Category: Toxin]] | ||
| + | [[Category: Two-loop backbone architecture]] | ||
Revision as of 17:58, 20 October 2021
alpha RgIA, a Novel Conotoxin that Blocks the alpha9-alpha10 nAChR
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