What’s a Spider? Designation of the Neotype for the First Animal Species Ever Described, Araneus angulatus Clerck 1757 (Araneae: Araneidae)

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  What’s a Spider? Designation of the Neotype for the First Animal Species Ever Described, Araneus angulatus Clerck 1757 (Araneae: Araneidae) Abstract We designate a neotype for the Eurasian spider species Araneus angulatus Clerck, 1757, thereby fixing the objective application of the species name, the genus name Araneus Clerck 1757, the family name Araneidae Clerck 1757, and the superfamily name Araneoidea Clerck 1757. By etymology and arachnological tradition, it also unofficially fixes the application of the ordinal name Araneae Clerck 1757 and thus answers the uncontroversial question, “What’s a spider?” A. angulatus also happens to be historically the first animal species ever described because Clerck (1757) has priority over Linnaeus (1758). Neotype designation is justified for three reasons: the syntypes of A. angulatus are lost; “ A. angulatus ” contains significant COI sequence divergence, potentially representing intraspecific variation, misidentifications, or as many...

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;