Preparation and Functional Identification of a Novel Conotoxin QcMNCL-XIII0.1 from Conus quercinus

Toxins (Basel). 2022 Jan 26;14(2):99. doi: 10.3390/toxins14020099.

Abstract

Conotoxins are tools used by marine Conus snails to hunt and are a significant repository for marine drug research. Conotoxins highly selectively coordinate different subtypes of various ion channels, and a few have been used in pain management. Although more than 8000 conotoxin genes have been found, the biological activity and function of most have not yet been examined. In this report, we selected the toxin gene QcMNCL-XIII0.1 from our previous investigation and studied it in vitro. First, we successfully prepared active recombinant QcMNCL-XIII0.1 using a TrxA (Thioredoxin A)-assisted folding expression vector based on genetic engineering technology. Animal experiments showed that the recombinant QcMNCL-XIII0.1 exhibited nerve conduction inhibition similar to that of pethidine hydrochloride. With flow cytometry combined fluorescent probe Fluo-4 AM, we found that 10 ng/μL recombinant QcMNCL-XIII0.1 inhibited the fluorescence intensity by 31.07% in the 293T cell model transfected with Cav3.1, implying an interaction between α1G T-type calcium channel protein and recombinant QcMNCL-XIII0.1. This toxin could be an important drug in biomedical research and medicine for pain control.

Keywords: CACNA1G; Conus; T-type calcium channel; conotoxin; pethidine; α1G.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / physiology*
  • Cell Line
  • Conotoxins / genetics
  • Conotoxins / toxicity*
  • Conus Snail
  • Electric Stimulation
  • Humans
  • Neural Conduction / drug effects*
  • Rana catesbeiana
  • Recombinant Proteins / toxicity
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / physiology

Substances

  • CACNA1G protein, human
  • Calcium Channels, T-Type
  • Conotoxins
  • Recombinant Proteins