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2p4l

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Revision as of 07:19, 22 August 2018

Structure and sodium channel activity of an excitatory I1-superfamily conotoxin

Structural highlights

2p4l is a 1 chain structure with sequence from Conra. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Buczek O, Wei D, Babon JJ, Yang X, Fiedler B, Chen P, Yoshikami D, Olivera BM, Bulaj G, Norton RS. Structure and sodium channel activity of an excitatory I1-superfamily conotoxin. Biochemistry. 2007 Sep 4;46(35):9929-40. Epub 2007 Aug 14. PMID:17696362 doi:10.1021/bi700797f
↑ Fiedler B, Zhang MM, Buczek O, Azam L, Bulaj G, Norton RS, Olivera BM, Yoshikami D. Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of voltage-gated sodium channels Na(V)1.2, 1.6 and 1.7. Biochem Pharmacol. 2008 Jun 15;75(12):2334-44. doi: 10.1016/j.bcp.2008.03.019., Epub 2008 Apr 6. PMID:18486102 doi:http://dx.doi.org/10.1016/j.bcp.2008.03.019
↑ Buczek O, Wei D, Babon JJ, Yang X, Fiedler B, Chen P, Yoshikami D, Olivera BM, Bulaj G, Norton RS. Structure and sodium channel activity of an excitatory I1-superfamily conotoxin. Biochemistry. 2007 Sep 4;46(35):9929-40. Epub 2007 Aug 14. PMID:17696362 doi:10.1021/bi700797f

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p4l"

@@ Line 1: / Line 1: @@
 ==Structure and sodium channel activity of an excitatory I1-superfamily conotoxin==
 <StructureSection load='2p4l' size='340' side='right' caption='[[2p4l]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2p4l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Conra Conra]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P4L FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p4l OCA], [http://pdbe.org/2p4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p4l RCSB], [http://www.ebi.ac.uk/pdbsum/2p4l PDBsum]</span></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=2p4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p4l OCA], [http://pdbe.org/2p4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p4l RCSB], [http://www.ebi.ac.uk/pdbsum/2p4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p4l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p4/2p4l_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p4/2p4l_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2p4l ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2p4l

From Proteopedia

Revision as of 07:19, 22 August 2018

Structure and sodium channel activity of an excitatory I1-superfamily conotoxin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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