1tyk

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Revision as of 08:52, 21 March 2018

SOLUTION STRUCTURE OF A TOXIN FROM THE TARANTULA, GRAMMOSTOLA SPATULATA, WHICH INHIBITS MECHANOSENSITIVE ION CHANNELS

Structural highlights

1tyk is a 1 chain structure with sequence from Grammostola rosea. This structure supersedes the now removed PDB entry 1lqr. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1lqr
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MTX4_GRARO] This cationic hydrophobic peptide inhibits a lot of different channels and has an antimicrobial activity. It blocks mechanosensitive ion channels (also named stretch-activated channels or SACs), without having effect on whole-cell voltage-sensitive currents. Acts by partitioning into the membrane and perturbing the interface between the channel and the lipid bilayer without necessarily being in physical contact with the channel. Inhibits atrial fibrillation as well as the membrane motor of outer hair cells at low doses. It also binds to the voltage sensor of voltage-gated potassium channels from the archaebacterium Aeropyrum pernix (KvAP) without affecting channel gating. It has also a medium toxicity on a large spectra of sodium channels (Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A), and also inhibits potassium channels Kv11.1/KCNH2 and Kv11.2/KCNH6. It also exhibits antimicrobial activities against the Gram-positive bacteria B.subtilis (MIC=0.5 uM), S.aureus (MIC=2-4 uM), and S.epidermidis (MIC=4-8 uM), and Gram-negative bacteria S.typhimurium (MIC=32.64 uM), P.aeruginosa (MIC=8-16 uM), and E.coli (MIC=8-16 uM).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

Mechanosensitive channels (MSCs) play key roles in sensory processing and have been implicated as primary transducers for a variety of cellular responses ranging from osmosensing to gene expression. This paper presents the first structures of any kind known to interact specifically with MSCs. GsMTx-4 and GsMtx-2 are inhibitor cysteine knot peptides isolated from venom of the tarantula, Grammostola spatulata (Suchyna, T. M., Johnson, J. H., Hamer, K., Leykam, J. F., Gage, D. A., Clemo, H. F., Baumgarten, C. M., and Sachs, F. (2000) J. Gen. Physiol. 115, 583-598). Inhibition of cationic MSCs by the higher affinity GsMtx-4 (K(D) approximately 500 nm) reduced cell size in swollen and hypertrophic heart cells, swelling-activated currents in astrocytes, and stretch-induced arrhythmias in the heart. Despite the relatively low affinity, no cross-reactivity has been found with other channels. Using two-dimensional NMR spectroscopy, we determined the solution structure of GsMTx-4 and a lower affinity (GsMTx-2; K(D) approximately 6 microm) peptide from the same venom. The dominant feature of the two structures is a hydrophobic patch, utilizing most of the aromatic residues and surrounded with charged residues. The spatial arrangement of charged residues that are unique to GsMTx-4 and GsMTx-2 may underlie the selectivity of these peptides.

Solution structure of peptide toxins that block mechanosensitive ion channels.,Oswald RE, Suchyna TM, McFeeters R, Gottlieb P, Sachs F J Biol Chem. 2002 Sep 13;277(37):34443-50. Epub 2002 Jun 24. PMID:12082099^[10]

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

References

↑ Suchyna TM, Johnson JH, Hamer K, Leykam JF, Gage DA, Clemo HF, Baumgarten CM, Sachs F. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol. 2000 May;115(5):583-98. PMID:10779316
↑ Bode F, Sachs F, Franz MR. Tarantula peptide inhibits atrial fibrillation. Nature. 2001 Jan 4;409(6816):35-6. PMID:11343101 doi:http://dx.doi.org/10.1038/35051165
↑ Suchyna TM, Tape SE, Koeppe RE 2nd, Andersen OS, Sachs F, Gottlieb PA. Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. Nature. 2004 Jul 8;430(6996):235-40. PMID:15241420 doi:http://dx.doi.org/10.1038/nature02743
↑ 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
↑ Jung HJ, Kim PI, Lee SK, Lee CW, Eu YJ, Lee DG, Earm YE, Kim JI. Lipid membrane interaction and antimicrobial activity of GsMTx-4, an inhibitor of mechanosensitive channel. Biochem Biophys Res Commun. 2006 Feb 10;340(2):633-8. Epub 2005 Dec 19. PMID:16376854 doi:http://dx.doi.org/10.1016/j.bbrc.2005.12.046
↑ Fang J, Iwasa KH. Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells. Neurosci Lett. 2006 Aug 14;404(1-2):213-6. Epub 2006 Jun 22. PMID:16797839 doi:http://dx.doi.org/S0304-3940(06)00548-9
↑ Nishizawa M, Nishizawa K. Molecular dynamics simulations of a stretch-activated channel inhibitor GsMTx4 with lipid membranes: two binding modes and effects of lipid structure. Biophys J. 2007 Jun 15;92(12):4233-43. Epub 2007 Mar 23. PMID:17384064 doi:http://dx.doi.org/10.1529/biophysj.106.101071
↑ Posokhov YO, Gottlieb PA, Morales MJ, Sachs F, Ladokhin AS. Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers? Biophys J. 2007 Aug 15;93(4):L20-2. Epub 2007 Jun 15. PMID:17573432 doi:http://dx.doi.org/10.1529/biophysj.107.112375
↑ 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
↑ Oswald RE, Suchyna TM, McFeeters R, Gottlieb P, Sachs F. Solution structure of peptide toxins that block mechanosensitive ion channels. J Biol Chem. 2002 Sep 13;277(37):34443-50. Epub 2002 Jun 24. PMID:12082099 doi:10.1074/jbc.M202715200

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

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Retrieved from "http://52.214.119.220/wiki/index.php/1tyk"

@@ Line 1: / Line 1: @@
 ==SOLUTION STRUCTURE OF A TOXIN FROM THE TARANTULA, GRAMMOSTOLA SPATULATA, WHICH INHIBITS MECHANOSENSITIVE ION CHANNELS==
 <StructureSection load='1tyk' size='340' side='right' caption='[[1tyk]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1tyk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1lqr 1lqr]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TYK FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lqr|1lqr]]</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=1tyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tyk OCA], [http://pdbe.org/1tyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tyk RCSB], [http://www.ebi.ac.uk/pdbsum/1tyk 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=1tyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tyk OCA], [http://pdbe.org/1tyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tyk RCSB], [http://www.ebi.ac.uk/pdbsum/1tyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tyk ProSAT]</span></td></tr>
 </table>
 == Function ==

1tyk

From Proteopedia

Revision as of 08:52, 21 March 2018

SOLUTION STRUCTURE OF A TOXIN FROM THE TARANTULA, GRAMMOSTOLA SPATULATA, WHICH INHIBITS MECHANOSENSITIVE ION CHANNELS

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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