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Identification of sodium channel toxins from marine cone snails of the subgenera Textilia and Afonsoconus
Ist Teil von
Cellular and molecular life sciences : CMLS, 2023-10, Vol.80 (10), p.287-287, Article 287
Ort / Verlag
Cham: Springer International Publishing
Erscheinungsjahr
2023
Quelle
SpringerLink_现刊
Beschreibungen/Notizen
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.