Identification of sodium channel toxins from marine cone snails of the subgenera Textilia and Afonsoconus.

Autor: McMahon KL; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., O'Brien H; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA., Schroeder CI; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.; Peptide Therapeutics, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA., Deuis JR; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Venkatachalam D; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Huang D; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Green BR; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA., Bandyopadhyay PK; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA., Li Q; Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT, 84112, USA.; Cancer Bioinformatics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA., Yandell M; Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT, 84112, USA., Safavi-Hemami H; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA., Olivera BM; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA., Vetter I; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia., Robinson SD; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia. sam.robinson@uq.edu.au.; Biology Department, University of Utah, Salt Lake City, UT, 84112, USA. sam.robinson@uq.edu.au.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2023 Sep 09; Vol. 80 (10), pp. 287. Date of Electronic Publication: 2023 Sep 09.
DOI: 10.1007/s00018-023-04935-0
Abstrakt: Voltage-gated sodium (Na V ) channels are transmembrane proteins that play a critical role in electrical signaling in the nervous system and other excitable tissues. µ-Conotoxins are peptide toxins from the venoms of marine cone snails (genus Conus) that block Na V channels with nanomolar potency. Most species of the subgenera Textilia and Afonsoconus are difficult to acquire; therefore, their venoms have yet to be comprehensively interrogated for µ-conotoxins. The goal of this study was to find new µ-conotoxins from species of the subgenera Textilia and Afonsoconus and investigate their selectivity at human Na V channels. Using RNA-seq of the venom gland of Conus (Textilia) bullatus, we identified 12 µ-conotoxin (or µ-conotoxin-like) sequences. Based on these sequences we designed primers which we used to identify additional µ-conotoxin sequences from DNA extracted from historical specimens of species from Textilia and Afonsoconus. We synthesized six of these µ-conotoxins and tested their activity on human Na V 1.1-Na V 1.8. Five of the six synthetic peptides were potent blockers of human Na V channels. Of these, two peptides (BuIIIB and BuIIIE) were potent blockers of hNa V 1.3. Three of the peptides (BuIIIB, BuIIIE and AdIIIA) had submicromolar activity at hNa V 1.7. This study serves as an example of the identification of new peptide toxins from historical DNA and provides new insights into structure-activity relationships of µ-conotoxins with activity at hNa V 1.3 and hNa V 1.7.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: