8.B.10 The Psalmotoxin-1 (PcTx1) Family Psalmotoxin-1 is spider toxin that is selective and high affinity inhibitor of ASIC1a. PcTx1 inhibits ASIC1a homomers with an affinity of 0.7 nM without any effect on ASIC1a containing heteromers. It thus helped to characterize ASIC1a homomeric channels in peripheric and central neurons. PcTx1 acts as a gating modifier since it shifts the channel from the resting to an inactivated state by increasing its affinity for H(+) (Diochot et al., 2007). PcTx1 homologous to cystine knot toxin of Chilobrachys jingzhao (38% identity). The 3-d structure of PcTx1 has been solved by NMR (1LMM_A; Escoubas et al. 2003). The binding of PcTx1 to ASIC1a channels (1.A.6) depends on the β-sheet and β-turn linking and residues known to be implicated in channel recognition of other inhibitory cystine knot (ICK) toxins.
This family belongs to the Conotoxin Superfamily.
References:
A, J.Y., G.J. Wang, J.G. Sun, Y.C. Gu, M.S. Wu, and J.H. Liu. (2006). Identification of phase I and phase II metabolites of Guanfu base A hydrochloride in human urine. Eur J Drug Metab Pharmacokinet 28: 265-272.
Adão, R., R. Seixas, P. Gomes, J.C. Pessoa, and M. Bastos. (2008). Membrane structure and interactions of a short Lycotoxin I analogue. J Pept Sci 14: 528-534.
Chagot, B., P. Escoubas, E. Villegas, C. Bernard, G. Ferrat, G. Corzo, M. Lazdunski, and H. Darbon. (2004). Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus. Protein. Sci. 13: 1197-1208.
Chagot, B., P. Escoubas, S. Diochot, C. Bernard, M. Lazdunski, and H. Darbon. (2005). Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels. Protein. Sci. 14: 2003-2010.
Diochot, S., M. Salinas, A. Baron, P. Escoubas, and M. Lazdunski. (2007). Peptides inhibitors of acid-sensing ion channels. Toxicon 49: 271-284.
Escoubas, P., C. Bernard, G. Lambeau, M. Lazdunski, and H. Darbon. (2003). Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein. Sci. 12: 1332-1343.
Hughes, S.R., P.F. Dowd, R.E. Hector, T. Panavas, D.E. Sterner, N. Qureshi, K.M. Bischoff, S.S. Bang, J.A. Mertens, E.T. Johnson, X.L. Li, J.S. Jackson, R.J. Caughey, S.B. Riedmuller, S. Bartolett, S. Liu, J.O. Rich, P.J. Farrelly, T.R. Butt, J. Labaer, and M.A. Cotta. (2008). Lycotoxin-1 insecticidal peptide optimized by amino acid scanning mutagenesis and expressed as a coproduct in an ethanologenic Saccharomyces cerevisiae strain. J Pept Sci 14: 1039-1050.
Santos, D.M., R.M. Verly, D. Piló-Veloso, M. de Maria, M.A. de Carvalho, P.S. Cisalpino, B.M. Soares, C.G. Diniz, L.M. Farias, D.F. Moreira, F. Frézard, M.P. Bemquerer, A.M. Pimenta, and M.E. de Lima. (2010). LyeTx I, a potent antimicrobial peptide from the venom of the spider Lycosa erythrognatha. Amino Acids 39: 135-144.
Yu, H., L. Yang, L. Liu, X. Zhao, and X. Huang. (2017). Molecular dynamics simulations investigate the Mechanism of Psalmotoxin 1 regulating gating process of an Acid-sensing ion channel 1a at pH 5.5. J Biomol Struct Dyn 1-21. [Epub: Ahead of Print]
Examples:
TC#	Name	Organismal Type	Example
8.B.10.1.1	Psalmotoxin-1 (PcTx1) 40 aas (Diochot et al., 2007). The Pi theraphotoxin Pc1a potently and selectively blocks the acid-sensing ion channel ASIC1a/ACCN2. The blockade is rapid and reversible. Psalmotoxin 1 loses its capacity to block ASIC1a/ACCN2 as soon as this subunit is associated with another member of the family (ASIC2a/ACCN1 or ASIC3/ACCN3). The toxin can distinguish between the two ASIC1/ACCN2 splice variants ASIC1a/ACCN2 and ASIC1b/ACCN2 (Chagot et al. 2004). The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. The 3-D structure is known (Chagot et al. 2005). This "gating blocker" mainly regulate ASIC1a gating through hydrogen bonds, which can affect the relative positions of several key domains in ASIC1a, and a long-range conformational change path was determined, which is composed of beta1, beta2, beta10, alpha6, alpha7, beta11 and beta12 in ASIC1a (Yu et al. 2017).	Spiders	*PcTx1 of Psalmopoeus cambridgei* (P60514)**

8.B.10.1.2	Unprocessed precursor of U34-theraphotoxin-Cj1a; Jingzhaotoxin-74; JzTx-74 of 134 aas. The processed form is secreted. Belongs to the MIT-like AcTx family.	Spiders	*JzTx-74 of Chilobrachys guangxiensis* (Chinese earth tiger tarantula) (Chilobrachys jingzhao)**

8.B.10.1.3	U33-theraphotoxin-Cj1a; Jingzhaotoxin-69, JzTx69, or 124 aas.	Animals	JzTx69 of Chilobrachys guangxiensis

8.B.10.1.4	U1-hexatoxin-Hsp201e; Atracotoxin-Hs20f7496	Animals	Atracotoxin of Hadronyche sp. 20

8.B.10.1.5	Hainantoxin-XIV-4 of 84 aas. Of the MIT-like AcTx family.	Animal	Hainantoxin-XIV-4 of Haplopelma hainanum

Examples:
TC#	Name	Organismal Type	Example
8.B.10.2.1	M-Lycotoxin Hc1a; Lycotoxin I of 25 aas. Forms pores that permeabilize the cell membrane and promotes efflux of calcium from synaptosomes. It also causes hemolysis and dissipates voltage gradients across muscle membrane. Potently inhibits the growth of bacteria, yeast and Leishmania. Is lethal to lepidopteran larvae. May function both in the prey capture strategy and in protection from infectious organisms arising from prey ingestion (Hughes et al. 2008; Adão et al. 2008).	Spiders	*Lycotoxin I of Hogna (Lycosa) carolinensis* (wolf spider)**

8.B.10.2.2	Short cationic peptide 5a, SCP5a of 24 aas. 46% identical to M-Lycotoxin Hc1a (8.B.10.2.1)	Animals	*SCP5a of Cupiennius salei* (spider)**

8.B.10.2.3	Toxin LyeTx 1 of 26 aas. It has antimicrobial activity against the Gram-positive bacterium, S. aureus (MIC=3.79 µM), the Gram-negative bacterium, E. coli (MIC=7.81 µM) and the yeasts, C. krusei (MIC=26.3 µM) and C. neoformans (MIC=13.2 µM). It also has hemolytic activity against rabbit erythrocytes and forms pores in lipid bilayers in vitro; pore formation is reduced when cholesterol is present in the bilayers (Santos et al. 2010). The x-ray structure is known (6CL3_A).		Toxin LyeTx of Lycosa erythrognatha (Wolf spider) (Scaptocosa raptoria)

8.B.10.2.4	Putative mature peptide toxin-like CIGES of 114 aas.		Toxin of Pelinobius muticus

Examples:
TC#	Name	Organismal Type	Example
8.B.10.3.1	Conopressin/conophysin conotoxin of 125 aas and 1 N-terminal TMS. It targets vasopressin receptors (Robinson and Norton 2014).		Conopressin of Conus monile

8.B.10.3.2	Vasotocin-neurophysin, partial, of 104 aas		Neurophysin of Scylla paramamosain

8.B.10.3.3	Arg-vassopressin-like peptide of 149 aas		Vassopressin-like peptide of Laodelphax striatellus