Spider Toxin Card | ArachnoServer

Toxin Name	M-theraphotoxin-Gr1a
Source Species	*Grammostola rosea* (Chilean rose tarantula)
Toxin Group	Theraphotoxin
Description	Toxin blocks mechanosensitive ion channels (also named strech-activated channels or SACs), without having a significant effect on whole-cell voltage-sensitive currents. The toxin acts by partitioning into the membrane and altering bilayer mechanics close to the channel. The toxin also binds to the voltage sensor of voltage-gated potassium channels from the archaebacterium Aeropyrum pernix (KvAP) without affecting channel gating. The toxin inhibits atrial fibrillation as well as the membrane motor of outer hair cells. The toxin exhibits antimicrobial activity, being more active against Gram-positive than Gram-negative bacteria.
Discovered	2000

Sex: female, Prosoma length: 26mm
Photo courtesy of Bastian Rast
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This toxin last updated on Aug 19, 2014

Taxonomy

Biological Activity

Antimicrobial

Neurotoxin

Molecular Target	IC50	Kd	Comment
Sodium channel, voltage-gated (vertebrate): Na_V1.1	12100.0 nM		HEK293 cells expressing human channel
Mechanosensitive ion channel: Eukaryotic mechanosensitive channel		630.0 nM	Toxin blocks mechanosensitive channels (= strech-activated channels) in rat astrocytes,
Sodium channel, voltage-gated (vertebrate): Na_V1.2	8100.0 nM		HEK293 cells expressing human channel
Sodium channel, voltage-gated (vertebrate): Na_V1.3	14100.0 nM		HEK293 cells expressing human channel
Sodium channel, voltage-gated (vertebrate): Na_V1.4	11900.0 nM		HEK293 cells expressing human channel
Sodium channel, voltage-gated (vertebrate): Na_V1.5	12200.0 nM		HEK293 cells expressing human channel
Sodium channel, voltage-gated (vertebrate): Na_V1.6	8600.0 nM		HEK293 cells expressing human channel
Sodium channel, voltage-gated (vertebrate): Na_V1.7	7400.0 nM		HEK293 cells expressing human channel

Taxon	ED50	LD50	PD50	Qualitative Information
Bacillus subtilis				0.5 μM = minimal inhibitory concentration
Staphylococcus epidermidis				4-8 μM = minimal inhibitory concentration
Staphylococcus aureus				2-4 μM = minimal inhibitory concentration
Pseudomonas aeruginosa				8-16 μM = minimal inhibitory concentration
Salmonella typhimurium				32.64 μM = minimal inhibitory concentration
Escherichia coli				8-16 μM = minimal inhibitory concentration

Accessions

Literature References

Original Deposition References
Suchyna T.M., Johnson J.H., Hamer K., Leykam J.F., Gage D.A., Clemo H.F., Baumgarten C.M., Sachs F. J. Gen. Physiol. 115:583-598(2000). Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels.
Ostrow K.L., Mammoser A., Suchyna T.M., Sachs F., Oswald R.E., Kubo S., Chino N., Gottlieb P.A. Toxicon 42:263-274(2003). cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels.
Other References
Kimura T., Kubo T. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. Grammostola spatulata venom gland cDNA.
Bode F., Sachs F., Franz M.R. Nature 409:35-36(2001). Tarantula peptide inhibits atrial fibrillation.
Oswald R.E., Suchyna T.M., McFeeters R., Gottlieb P.A., Sachs F. J. Biol. Chem. 277:34443-34450(2002). Solution structure of peptide toxins that block mechanosensitive ion channels.
Ruta V., MacKinnon R. Biochemistry 43:10071-10079(2004). Localization of the voltage-sensor toxin receptor on KvAP.
Suchyna T.M., Tape S.E., Koeppe R.E. II, Andersen O.S., Sachs F., Gottlieb P.A. Nature 430:235-240(2004). Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers.
Fang J., Iwasa K.H. Neurosci. Lett. 404:213-216(2006). Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells.
Jung H.J., Kim P.I., Lee S.K., Lee C.W., Eu Y.J., Lee D.G., Earm Y.E., Kim J.I. Biochem. Biophy. Res. Comm. 340:633-638(2006) Lipid membrane interaction and antimicrobial activity of GsMTx-4, an inhibitor of mechanosensitive channel.
Sachs F., Suchyna T.M., Gottlieb P.A. Patent number WO 2006/014493 A2, 9-FEB-2006. Mechanically activated channel blocker
Sachs F., Suchyna T.M., Johnson J. Patent number US7125847, 24-OCT-2006. Mechanically activated channel blocker
Bowman C.L., Gottlieb P.A., Suchyna T.M., Murphy Y.K., Sachs F. Toxicon. 49:249-270(2007) Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: history, properties, mechanisms and pharmacology.
Nishizawa M., Nishizawa K. Biophysical Journal 92:4233-4243(2007) Molecular dynamics simulations of a stretch-activated channel inhibitor GsMTx4 with lipid membranes: two binding modes and effects of lipid structure.
Posokhov Y.O., Gottlieb P.A., Morales M.J., Sachs F., Ladokhin A.S. Biophysical Journal 93:20-22(2007) Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers?
Sachs F., Suchyna T.M., Gottlieb P.A. Patent number US 7259145, 21-AUG-2007. Mechanically activated channel blocker
Redaelli E., Cassulini R.R., Silva D.F., Clement H., Schiavon E., Zamudio F.Z., Odell G., Arcangeli A., Clare J.J., Alagón A., de la Vega R.C., Possani L.D., Wanke E. J. Biol. Chem. 285:4130-42(2010) Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels.

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