2jry: Difference between revisions
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< | ==Structure and Sodium Channel Activity of an Excitatory I1-Superfamily Conotoxin== | ||
<StructureSection load='2jry' size='340' side='right'caption='[[2jry]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jry]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_radiatus Conus radiatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JRY FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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=2jry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jry OCA], [https://pdbe.org/2jry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jry RCSB], [https://www.ebi.ac.uk/pdbsum/2jry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jry ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/CI1BA_CONRA CI1BA_CONRA]] Iota-conotoxins bind to voltage-gated sodium channels and act as agonists by shifting the voltage-dependence of activation to more hyperpolarized levels. This toxin acts on Nav1.6/SCN8A > Nav1.2/SCN2A > Nav1.7/SCN9A sodium channels. Produces general excitatory symptoms upon intracorporeal injection and repetitive action potentials in the frog cutaneous pectoris muscle. Natural peptide (with D-Phe) is active on nerve, but not on muscle. Synthetic peptide (with L-Phe) is not active on both nerve and muscle.<ref>PMID:17696362</ref> <ref>PMID:18486102</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jr/2jry_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jry ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Conotoxin iota-RXIA, from the fish-hunting species Conus radiatus, is a member of the recently characterized I1-superfamily, which contains eight cysteine residues arranged in a -C-C-CC-CC-C-C- pattern. iota-RXIA (formerly designated r11a) is one of three characterized I1 peptides in which the third last residue is posttranslationally isomerized to the d configuration. Naturally occurring iota-RXIA with d-Phe44 is significantly more active as an excitotoxin than the l-Phe analogue both in vitro and in vivo. We have determined the solution structures of both forms by NMR spectroscopy, the first for an I1-superfamily member. The disulfide connectivities were determined from structure calculations and confirmed chemically as 5-19, 12-22, 18-27, and 21-38, suggesting that iota-RXIA has an ICK structural motif with one additional disulfide (21-38). Indeed, apart from the first few residues, the structure is well defined up to around residue 35 and does adopt an ICK structure. The C-terminal region, including Phe44, is disordered. Comparison of the d-Phe44 and l-Phe44 forms indicates that the switch from one enantiomer to the other has very little effect on the structure, even though it is clearly important for receptor interaction based on activity data. Finally, we identify the target of iota-RXIA as a voltage-gated sodium channel; iota-RXIA is an agonist, shifting the voltage dependence of activation of mouse NaV1.6 expressed in Xenopus oocytes to more hyperpolarized potentials. Thus, there is a convergence of structure and function in iota-RXIA, as its disulfide pairing and structure resemble those of funnel web spider toxins that also target sodium channels. | |||
Structure and sodium channel activity of an excitatory I1-superfamily conotoxin.,Buczek O, Wei D, Babon JJ, Yang X, Fiedler B, Chen P, Yoshikami D, Olivera BM, Bulaj G, Norton RS Biochemistry. 2007 Sep 4;46(35):9929-40. Epub 2007 Aug 14. PMID:17696362<ref>PMID:17696362</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jry" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Conus radiatus]] | [[Category: Conus radiatus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Babon, J | [[Category: Babon, J]] | ||
[[Category: Buczek, O | [[Category: Buczek, O]] | ||
[[Category: Bulaj, G | [[Category: Bulaj, G]] | ||
[[Category: Chen, P | [[Category: Chen, P]] | ||
[[Category: Fiedler, B | [[Category: Fiedler, B]] | ||
[[Category: Norton, R | [[Category: Norton, R]] | ||
[[Category: Olivera, B | [[Category: Olivera, B]] | ||
[[Category: Wei, D | [[Category: Wei, D]] | ||
[[Category: Yang, X | [[Category: Yang, X]] | ||
[[Category: Yoshikami, D | [[Category: Yoshikami, D]] | ||
[[Category: Iota-conotoxin]] | [[Category: Iota-conotoxin]] | ||
[[Category: Toxin]] | |||