8.B.30.  The Diguetoxin (Diguetoxin) Family

Insecticidal toxins frequently target voltage-gated cation channels (TC# 1.A.1) (Krapcho et al. 1995, Bloomquist et al. 1996). One such toxin, Dc1a, promotes opening of insect Nav channels. The toxin binds to the S1-S2 and S3-S4 loops in the domain II voltage-sensor (i.e., receptor site 4). The American cockroach P.americana is largely resistant to the effects of this toxin due to an unusual sequence within the domain II S1-S2 loop. In vivo, the toxin paralyzes lepidopteran and dipteran larvae. Paralyzed insects ultimately die from secondary effects of starvation and dehydration (Bende et al. 2014). The toxin has no effect on the human Nav channel subtypes Nav1.1 - Nav1.7, and has no effect on hERG (Kv11.1) and Kv2.1. It is non-toxic to mice (Bende et al. 2014).


 


 

References:

Bende, N.S., S. Dziemborowicz, M. Mobli, V. Herzig, J. Gilchrist, J. Wagner, G.M. Nicholson, G.F. King, and F. Bosmans. (2014). A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. Nat Commun 5: 4350.
Bloomquist, J.R., L.P. Kinne, V. Deutsch, and S.F. Simpson. (1996). Mode of action of an insecticidal peptide toxin from the venom of a weaving spider (Diguetia canities). Toxicon 34: 1072-1075.
Krapcho, K.J., R.M. Kral, Jr, B.C. Vanwagenen, K.G. Eppler, and T.K. Morgan. (1995). Characterization and cloning of insecticidal peptides from the primitive weaving spider Diguetia canities. Insect Biochem Mol Biol 25: 991-1000.
Shen, H., Z. Li, Y. Jiang, X. Pan, J. Wu, B. Cristofori-Armstrong, J.J. Smith, Y.K.Y. Chin, J. Lei, Q. Zhou, G.F. King, and N. Yan. (2018). Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science 362:.
Examples:

TC#NameOrganismal TypeExample
8.B.30.1.1

Mu-diguetoxin, Dc1a, of 94 aas and 1 N-terminal TMS that is cleaved off to generate the active toxin. The structure of a short Mu-DGTX-Dc1a has been determined (PDB# 2MI5; Shen et al. 2018). Alt name: DTX9.2. A short, processed, active toxin is 57 aas in length.

Dc1a of Diguetia canities (Desert bush spider) (Segestria canities)

 
8.B.30.1.2

Toxin homologue, Dc1b, of 57 aas.

Dc1b of Diguetia canities (Desert bush spider) (Segestria canities)

 
8.B.30.1.3

Toxin, Dc1c of 61 aas.

Dc1c of Dc1b of Diguetia canities (Desert bush spider) (Segestria canities)