Cell Mol Life Sci, 2025, 82(1):300

Spider venom peptides with unique fold selectively block Shaker-type potassium channels

Natural toxins are highly effective at targeting ion channels with high selectivity and potency. To date, all identified spider venom peptide toxins that modulate voltage-gated potassium (K) channels inhibit Shab (K2) or Shal-related isoforms (K4) by interacting with their voltage-sensing domains. In this study, we report novel spider-derived pore-blocking toxins that selectively target Shaker-type (K1) channels with nanomolar potency. We isolated murinotoxins MnTx-1 and MnTx-2 from the orange baboon tarantula Pterinochilus murinus and sequenced them using a combination of Edman degradation, mass spectrometry, and venom gland nanopore transcriptomics. MnTx-1 was produced recombinantly, and its NMR solution structure was determined. Although MnTx-1 shares sequence motifs common to spider toxins, it displays a distinctly different three-dimensional structure, featuring an alternative disulfide linkage, which we have termed the Disulfide-Reined Hairpin (DRH). We attribute the unique pharmacology of MnTx-1 to its unusual spatial structure. The DRH motif represents a promising new miniature scaffold for future bioengineering applications.

Kuzmenkov AI, Iunusova VA, Lushpa VA, Deyev YA, Babenko VV, Osipov DV, Berkut AA, Tytgat J, Bocharov EV, Adams DJ, Finol-Urdaneta RK, Vassilevski AA

IBCH: 12063
Ссылка на статью в журнале: https://link.springer.com/10.1007/s00018-025-05778-7
Кол-во цитирований на 06.2026: 1
Данные статьи проверены модераторами 2025-10-14

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