| |
| Toxin Name |
π-theraphotoxin-Pc1a |
| Source Species |
Psalmopoeus cambridgei (Trinidad chevron tarantula) |
| Toxin Group |
Theraphotoxin |
| Description |
π-TRTX-Pc1a potently and selectively blocks the proton-gated sodium channel ASIC1a (acid-sensitive ion channel 1a). The blockade is rapid and reversible. The toxin increases the affinity of ASIC1a for protons. π-TRTX-Pc1a loses its capacity to block ASIC1a as soon as this subunit is associated with another member of the ASIC family (ASIC2a or ASIC3). The toxin can distinguish between the two ASIC1 splice variants ASIC1a and ASIC1b. For ASIC1b, the toxin binds most tightly to the open state, promoting opening, whereas for ASIC1a, it binds most tightly to the open and desensitized state, promoting desensitization. The toxin binds to the cysteine rich domains (CRD I and CRD II) of the extracellular region of the ASIC1a channel. |
| Discovered |
2000 |
|
Sex: Female, Prosoma length: 25mm
Photo courtesy of Bastian Rast
Use of photo governed by creative
commons noncommercial license
|
| This toxin last updated on Jul 21, 2010 |
|
| Current Taxonomy |
Historic Taxonomy |
| Kingdom |
Animalia |
| Phylum |
Arthropoda |
| Class |
Arachnida |
| Order |
Araneae |
| Infra-order |
Mygalomorphae |
| Family |
Theraphosidae |
| Genus |
Psalmopoeus |
| Species |
cambridgei |
|
| Psalmopoeus cambridgei |
| Psalmopoeus cambridgii |
| Santaremia longipes |
|
|
| Molecular Target |
ED50 |
IC50 |
Kd |
Pharmacophore |
Comment |
| Acid-sensing ion channel (ASIC): ASIC1a/b |
|
0.7
nM
|
|
|
Specific inhibition of ASIC1a channels expressed in oocytes by synthetic toxin. Also blocks native channels expressed in DRG cells (IC50=0.9 nM) |
| Taxon |
ED50 |
LD50 |
PD50 |
Qualitative Information |
| Mus musculus |
|
|
|
0.1 nmol of the toxin had potent analgesic properties against thermal, mechanical, chemical, inflammatory and neuropathic pain
|
|
| Source |
Accession |
| ArachnoServer
|
AS000400 |
| NCBI_Taxon
|
179874
|
| PDB
|
1LMM
|
| UniProt
|
P60514
|
|
| Original Deposition References |
Escoubas P., de Weille J.R., Lecoq A., Diochot S., Waldmann R., Champigny G., Moinier D., Menez A., Lazdunski M.
J. Biol. Chem. 275:25116-25121(2000).
Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
|
Escoubas P., Bernard C., Lambeau G., Lazdunski M., Darbon H.
Protein Sci. 12:1332-1343(2003).
Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels.
|
| Other References |
Chen X., Kalbacher H., Gründer S.
J. Gen. Physiol. 126:71-79(2005).
The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.
|
Chen X., Kalbacher H., Gründer S.
J. Gen. Physiol. 127:267-276(2006).
Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent.
|
Salinas M., Rash L.D., Baron A., Lambeau G., Escoubas P., Lazdunski M.
J. Physiol. (Lond.) 570:339-354(2006).
The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a.
|
Lazdunski M., Escoubas P., DeWeille J., Diochot S.
Patent number US 7132505, 07-NOV-2006.
Polypeptide inhibiting a proton-gated Na+ channel, a nucleic acid coding for such polypeptide and a method of manufacturing an ASIC1a channel blocker
|
Mazzuca M., Heurteaux C., Alloui A., Diochot S., Baron A., Voilley N., Blondeau N., Escoubas P., Gélot A., Cupo A., Zimmer A., Zimmer A.M., Eschalier A., Lazdunski M.
Nat. Neurosci. 10:943-945(2007).
A tarantula peptide against pain via ASIC1a channels and opioid mechanisms.
|
|
| Disulfide Bonds |
| Left Residue |
Right Residue |
Evidence |
| 3 |
18 |
Experimentally determined |
| 10 |
23 |
Experimentally determined |
| 17 |
33 |
Experimentally determined |
|
|
| Peptide Sequences |
>as:π-theraphotoxin-Pc1a|sp:P60514 Toxin from venom of the spider Psalmopoeus cambridgei that inhibits ASIC1a channels EDCIPKWKGCVNRHGDCCEGLECWKRRRSFEVCVPKTPKT |
Full BLAST |
BLAST mature toxin only
|
|
| Synonym |
Type |
| π-theraphotoxin-Pc1a |
Recommended full name |
| π-TRTX-Pc1a |
Recommended abbreviation |
| Psalmotoxin-1 |
Synonym |
| PcTx1 |
Synonym (abbreviation) |
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