Protoxin-I


Protoxin-I, also known as ProTx-I, or Beta/omega-theraphotoxin-Tp1a, is a 35-amino-acid peptide neurotoxin extracted from the venom of the tarantula Thrixopelma pruriens. Protoxin-I belongs to the inhibitory cystine knot (ICK) family of peptide toxins, which have been known to potently inhibit voltage-gated ion channels. Protoxin-I selectively blocks low voltage threshold T-type calcium channels,[1][2] voltage gated sodium channels[3][4] and the nociceptor cation channel TRPA1.[5] Due to its unique ability to bind to TRPA1, Protoxin-I has been implicated as a valuable pharmacological reagent with potential applications in clinical contexts with regards to pain and inflammation[5]

  1. ^ Ohkubo, Tsuyako; Yamazaki, Jun; Kitamura, Kenji (2010). "Tarantula Toxin ProTx-I Differentiates Between Human T-type Voltage-Gated Ca2+ Channels Cav3.1 and Cav3.2". Journal of Pharmacological Sciences. 112 (4): 452–458. doi:10.1254/jphs.09356FP. PMID 20351484. S2CID 29721634.
  2. ^ Bladen, Chris; Hamid, Jawed; Souza, Ivana A.; Zamponi, Gerald W. (2014-05-09). "Block of T-type calcium channels by protoxins I and II". Molecular Brain. 7 (1): 36. doi:10.1186/1756-6606-7-36. ISSN 1756-6606. PMC 4030284. PMID 24886690.
  3. ^ Middleton, Richard E.; Warren, Vivien A.; Kraus, Richard L.; Hwang, Jeremy C.; Liu, Chou J.; Dai, Ge; Brochu, Richard M.; Kohler, Martin G.; Gao, Ying-Duo; Garsky, Victor M.; Bogusky, Michael J. (2002-12-01). "Two Tarantula Peptides Inhibit Activation of Multiple Sodium Channels". Biochemistry. 41 (50): 14734–14747. doi:10.1021/bi026546a. ISSN 0006-2960. PMID 12475222.
  4. ^ Priest, Birgit T.; Blumenthal, Kenneth M.; Smith, Jaime J.; Warren, Vivien A.; Smith, McHardy M. (2007-02-01). "ProTx-I and ProTx-II: Gating modifiers of voltage-gated sodium channels". Toxicon. Gating Modifier Peptides of Ion Channels. 49 (2): 194–201. doi:10.1016/j.toxicon.2006.09.014. ISSN 0041-0101. PMID 17087985.
  5. ^ a b Gui, Junhong; Liu, Boyi; Cao, Guan; Lipchik, Andrew M.; Perez, Minervo; Dekan, Zoltan; Mobli, Mehdi; Daly, Norelle L.; Alewood, Paul F.; Parker, Laurie L.; King, Glenn F. (2014-03-03). "A Tarantula-Venom Peptide Antagonizes the TRPA1 Nociceptor Ion Channel by Binding to the S1–S4 Gating Domain". Current Biology. 24 (5): 473–483. Bibcode:2014CBio...24..473G. doi:10.1016/j.cub.2014.01.013. ISSN 0960-9822. PMC 3949122. PMID 24530065. S2CID 7479469.