8BWB
Spider toxin Pha1b (PnTx3-6) from Phoneutria nigriventer targeting CaV2.x calcium channels and TRPA1 channel
Summary for 8BWB
| Entry DOI | 10.2210/pdb8bwb/pdb |
| NMR Information | BMRB: 34776 |
| Descriptor | Omega-ctenitoxin-Pn4a (1 entity in total) |
| Functional Keywords | toxin, spider toxin, neurotoxin, cystine-knot peptide, antagonist of cav2.x calcium channels and trpa1 channel |
| Biological source | Phoneutria nigriventer (Brazilian armed spider) |
| Total number of polymer chains | 1 |
| Total formula weight | 6055.09 |
| Authors | Mironov, P.A.,Chernaya, E.M.,Paramonov, A.S.,Shenkarev, Z.O. (deposition date: 2022-12-06, release date: 2023-06-21, Last modification date: 2024-11-20) |
| Primary citation | Lyukmanova, E.N.,Mironov, P.A.,Kulbatskii, D.S.,Shulepko, M.A.,Paramonov, A.S.,Chernaya, E.M.,Logashina, Y.A.,Andreev, Y.A.,Kirpichnikov, M.P.,Shenkarev, Z.O. Recombinant Production, NMR Solution Structure, and Membrane Interaction of the Ph alpha 1 beta Toxin, a TRPA1 Modulator from the Brazilian Armed Spider Phoneutria nigriventer . Toxins, 15:-, 2023 Cited by PubMed Abstract: Phα1β (PnTx3-6) is a neurotoxin from the spider venom, originally identified as an antagonist of two ion channels involved in nociception: N-type voltage-gated calcium channel (Ca2.2) and TRPA1. In animal models, Phα1β administration reduces both acute and chronic pain. Here, we report the efficient bacterial expression system for the recombinant production of Phα1β and its N-labeled analogue. Spatial structure and dynamics of Phα1β were determined via NMR spectroscopy. The -terminal domain (Ala1-Ala40) contains the inhibitor cystine knot (ICK or knottin) motif, which is common to spider neurotoxins. The -terminal α-helix (Asn41-Cys52) stapled to ICK by two disulfides exhibits the µs-ms time-scale fluctuations. The Phα1β structure with the disulfide bond patterns Cys1-5, Cys2-7, Cys3-12, Cys4-10, Cys6-11, Cys8-9 is the first spider knottin with six disulfide bridges in one ICK domain, and is a good reference to other toxins from the ctenitoxin family. Phα1β has a large hydrophobic region on its surface and demonstrates a moderate affinity for partially anionic lipid vesicles at low salt conditions. Surprisingly, 10 µM Phα1β significantly increases the amplitude of diclofenac-evoked currents and does not affect the allyl isothiocyanate (AITC)-evoked currents through the rat TRPA1 channel expressed in oocytes. Targeting several unrelated ion channels, membrane binding, and the modulation of TRPA1 channel activity allow for considering Phα1β as a gating modifier toxin, probably interacting with S1-S4 gating domains from a membrane-bound state. PubMed: 37368679DOI: 10.3390/toxins15060378 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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