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| - | {{Seed}} | |
| - | [[Image:1s6x.png|left|200px]] | |
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| - | <!-- | + | ==Solution structure of VSTx== |
| - | The line below this paragraph, containing "STRUCTURE_1s6x", creates the "Structure Box" on the page.
| + | <StructureSection load='1s6x' size='340' side='right'caption='[[1s6x]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1s6x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S6X FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1s6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s6x OCA], [https://pdbe.org/1s6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s6x RCSB], [https://www.ebi.ac.uk/pdbsum/1s6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s6x ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1s6x| PDB=1s6x | SCENE= }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/VSTX1_GRARO VSTX1_GRARO] Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP.<ref>PMID:15241419</ref> <ref>PMID:15287735</ref> <ref>PMID:17002285</ref> <ref>PMID:19955179</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | VSTx1 is a voltage sensor toxin from the spider Grammostola spatulata that inhibits KvAP, an archeabacterial voltage-activated K(+) channel whose X-ray structure has been reported. Although the receptor for VSTx1 and the mechanism of inhibition are unknown, the sequence of the toxin is related to hanatoxin (HaTx) and SGTx, two toxins that inhibit eukaryotic voltage-activated K(+) channels by binding to voltage sensors. VSTx1 has been recently shown to interact equally well with lipid membranes that contain zwitterionic or acidic phospholipids, and it has been proposed that the toxin receptor is located within a region of the channel that is submerged in the membrane. As a first step toward understanding the inhibitory mechanism of VSTx1, we determined the three-dimensional solution structure of the toxin using NMR. Although the structure of VSTx1 is similar to HaTx and SGTx in terms of molecular fold and amphipathic character, the detailed positions of hydrophobic and surrounding charged residues in VSTx1 are very different than what is seen in the other toxins. The amphipathic character of VSTx1, notably the close apposition of basic and hydrophobic residues on one face of the toxin, raises the possibility that the toxin interacts with interfacial regions of the membrane. We reinvestigated the partitioning of VSTx1 into lipid membranes and find that VSTx1 partitioning requires negatively charged phospholipids. Intrinsic tryptophan fluorescence and acrylamide quenching experiments suggest that tryptophan residues on the hydrophobic surface of VSTx1 have a diminished exposure to water when the toxin interacts with membranes. The present results suggest that if membrane partitioning is involved in the mechanism by which VSTx1 inhibits voltage-activated K(+) channels, then binding of the toxin to the channel would likely occur at the interface between the polar headgroups and the hydrophobic phase of the membrane. |
| | | | |
| - | ===Solution structure of VSTx===
| + | Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel.,Jung HJ, Lee JY, Kim SH, Eu YJ, Shin SY, Milescu M, Swartz KJ, Kim JI Biochemistry. 2005 Apr 26;44(16):6015-23. PMID:15835890<ref>PMID:15835890</ref> |
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| - | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <!--
| + | </div> |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_15835890}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 1s6x" style="background-color:#fffaf0;"></div> |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 15835890 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_15835890}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | [[Category: Grammostola rosea]] |
| - | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6X OCA].
| + | [[Category: Large Structures]] |
| - | | + | [[Category: Eu YJ]] |
| - | ==Reference== | + | [[Category: Jung HJ]] |
| - | Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel., Jung HJ, Lee JY, Kim SH, Eu YJ, Shin SY, Milescu M, Swartz KJ, Kim JI, Biochemistry. 2005 Apr 26;44(16):6015-23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15835890 15835890]
| + | [[Category: Kim JI]] |
| - | [[Category: Eu, Y J.]] | + | |
| - | [[Category: Jung, H J.]] | + | |
| - | [[Category: Kim, J I.]] | + | |
| - | [[Category: Double stranded antiparallel beta-sheet]] | + | |
| - | [[Category: Inhibitory cystine knot]] | + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:00:06 2008''
| + | |
| Structural highlights
Function
VSTX1_GRARO Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP.[1] [2] [3] [4]
Publication Abstract from PubMed
VSTx1 is a voltage sensor toxin from the spider Grammostola spatulata that inhibits KvAP, an archeabacterial voltage-activated K(+) channel whose X-ray structure has been reported. Although the receptor for VSTx1 and the mechanism of inhibition are unknown, the sequence of the toxin is related to hanatoxin (HaTx) and SGTx, two toxins that inhibit eukaryotic voltage-activated K(+) channels by binding to voltage sensors. VSTx1 has been recently shown to interact equally well with lipid membranes that contain zwitterionic or acidic phospholipids, and it has been proposed that the toxin receptor is located within a region of the channel that is submerged in the membrane. As a first step toward understanding the inhibitory mechanism of VSTx1, we determined the three-dimensional solution structure of the toxin using NMR. Although the structure of VSTx1 is similar to HaTx and SGTx in terms of molecular fold and amphipathic character, the detailed positions of hydrophobic and surrounding charged residues in VSTx1 are very different than what is seen in the other toxins. The amphipathic character of VSTx1, notably the close apposition of basic and hydrophobic residues on one face of the toxin, raises the possibility that the toxin interacts with interfacial regions of the membrane. We reinvestigated the partitioning of VSTx1 into lipid membranes and find that VSTx1 partitioning requires negatively charged phospholipids. Intrinsic tryptophan fluorescence and acrylamide quenching experiments suggest that tryptophan residues on the hydrophobic surface of VSTx1 have a diminished exposure to water when the toxin interacts with membranes. The present results suggest that if membrane partitioning is involved in the mechanism by which VSTx1 inhibits voltage-activated K(+) channels, then binding of the toxin to the channel would likely occur at the interface between the polar headgroups and the hydrophobic phase of the membrane.
Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel.,Jung HJ, Lee JY, Kim SH, Eu YJ, Shin SY, Milescu M, Swartz KJ, Kim JI Biochemistry. 2005 Apr 26;44(16):6015-23. PMID:15835890[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee SY, MacKinnon R. A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature. 2004 Jul 8;430(6996):232-5. PMID:15241419 doi:http://dx.doi.org/10.1038/nature02632
- ↑ Ruta V, MacKinnon R. Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry. 2004 Aug 10;43(31):10071-9. PMID:15287735 doi:http://dx.doi.org/10.1021/bi049463y
- ↑ Bemporad D, Sands ZA, Wee CL, Grottesi A, Sansom MS. Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of lipid bilayers. Biochemistry. 2006 Oct 3;45(39):11844-55. PMID:17002285 doi:http://dx.doi.org/10.1021/bi061111z
- ↑ Redaelli E, Cassulini RR, Silva DF, Clement H, Schiavon E, Zamudio FZ, Odell G, Arcangeli A, Clare JJ, Alagon A, de la Vega RC, Possani LD, Wanke E. Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels. J Biol Chem. 2010 Feb 5;285(6):4130-42. doi: 10.1074/jbc.M109.054718. Epub 2009, Dec 2. PMID:19955179 doi:http://dx.doi.org/10.1074/jbc.M109.054718
- ↑ Jung HJ, Lee JY, Kim SH, Eu YJ, Shin SY, Milescu M, Swartz KJ, Kim JI. Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel. Biochemistry. 2005 Apr 26;44(16):6015-23. PMID:15835890 doi:http://dx.doi.org/10.1021/bi0477034
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