The pholcid spiders of Tunisia (Araneae: Pholcidae): new species, new records, and deep COI divergence in Holocnemus reini

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  The pholcid spiders of Tunisia (Araneae: Pholcidae): new species, new records, and deep COI divergence in Holocnemus reini Abstract Tunisia features a rapid transition between Mediterranean and Saharan biogeographical zones, resulting in a high degree of environmental heterogeneity. Despite this ecological diversity, Tunisian spiders have received limited attention compared to those of neighboring Maghreb countries. Here we combine the results of recent collections in Tunisia focusing on Pholcidae with a comprehensive review of previously published information, resulting in a total of six genera and eleven species. We present first records of the genera Micropholcus Deeleman-Reinhold & Prinsen, 1987 and Spermophorides Wunderlich, 1992 for Tunisia, represented by four new species: M. kahinae Huber sp. nov., M. echebbii Huber sp. nov., S. nabilae Huber & Kmira sp. nov., S. bchirae Huber sp. nov.; in addition, we redescribe S. huberti (Senglet, 1973) from Tunisian specimens,...

Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I

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Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I

Abstract

Voltage-gated sodium channels (NaVs) selectively permit diffusion of sodium ions across the cell membrane and, in excitable cells, are responsible for propagating action potentials. One of the nine human NaV isoforms, NaV1.8, is a promising target for analgesics, and selective inhibitors are of interest as therapeutics. One such inhibitor, the gating-modifier peptide Protoxin-I derived from tarantula venom, blocks channel opening by shifting the activation voltage threshold to more depolarised potentials, but the structural basis for this inhibition has not previously been determined. Using monolayer graphene grids, we report the cryogenic electron microscopy structures of full-length human apo-NaV1.8 and the Protoxin-I-bound complex at 3.1 Angstrom and 2.8 Angstrom resolution, respectively. The apo structure shows an unexpected movement of the Domain I S4-S5 helix, and VSDI was unresolvable. We find that Protoxin-I binds to and displaces the VSDII S3-S4 linker, hindering translocation of the S4II helix during activation.

Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I
Bryan Neumann, Stephen McCarthy, Shane Gonen, bioRxiv 2024.08.27.609828;