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Review
. 2024 Jan 9;16(1):34.
doi: 10.3390/toxins16010034.

Diversity and Evolutionary Analysis of Venom Insulin Derived from Cone Snails

Qiqi Guo  1 , Meiling Huang  1 , Ming Li  1 , Jiao Chen  1 , Shuanghuai Cheng  1 , Linlin Ma  2 , Bingmiao Gao  1
Affiliations
Review

Diversity and Evolutionary Analysis of Venom Insulin Derived from Cone Snails

Qiqi Guo et al. Toxins (Basel). .

Abstract

Cone snails possess a diverse array of novel peptide toxins, which selectively target ion channels and receptors in the nervous and cardiovascular systems. These numerous novel peptide toxins are a valuable resource for future marine drug development. In this review, we compared and analyzed the sequence diversity, three-dimensional structural variations, and evolutionary aspects of venom insulin derived from different cone snail species. The comparative analysis reveals that there are significant variations in the sequences and three-dimensional structures of venom insulins from cone snails with different feeding habits. Notably, the venom insulin of some piscivorous cone snails exhibits a greater similarity to humans and zebrafish insulins. It is important to emphasize that these venom insulins play a crucial role in the predatory strategies of these cone snails. Furthermore, a phylogenetic tree was constructed to trace the lineage of venom insulin sequences, shedding light on the evolutionary interconnections among cone snails with diverse diets.

Keywords: cone snails; conoinsulin; diversity; insulin; phylogenetic analysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 3
Figure 3
Alignment of insulin in humans, zebrafish, and different insulin sequences in the venom of various Conus. MEGA 7.0.14 software was used to create insulin sequence alignments and perform amino acid alignments on all peptide sequences, where MUSCLE algorithm was chosen to intelligently align amino acids [69,70]. Genedoc 2.7 software was used to export the sequence in FASTA format. B-chains and A-chains are enclosed within red and purple boxes, respectively. The conserved cysteine residues and small amino acids are highlighted in yellow. Aliphatic and aromatic amino acids are in red and blue fonts, respectively, on a grey background. Amphoteric and polar groups are in red and black fonts, respectively, on a green background. Negatively and positively charged amino acids are shown on a blue background in green and red. Proline and glycine amino acids are shown on a red background in blue and green. The hydrophobic amino acids are highlighted in black. ZF-Ins represents zebrafish insulin and ILP represents insulin-like peptide from C. victoriae.
Figure 4
Figure 4
Comparison of the 3D structures of human insulin, zebrafish insulin, and conoinsulins. The cartoon representations of models of insulin variants are depicted, with A-chains and B-chains of each insulin in cyan and orange, respectively. The structures of human insulin (PDB 3I40) and Con-Ins G1(PDB 5JYQ) were sourced from the PDB database. Additional structures were obtained from AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/). Protein 3D structure is predicted using homology computational structure prediction modeling from amino acid sequence [79]. SWISS-MODEL, available through the Expasy web server or Deep View software (Swiss Pdb-Viewer), is a fully automated server for the homology modeling of protein structures. The homologous sequences with highest sequence identity were assigned as templates, and then cartoon mode was used to build the model.
Figure 1
Figure 1
Conus species exhibit variances in their predator-prey relationships. (A) Fish hunters. (B) Worm hunters. (C) Mollusk hunters.
Figure 2
Figure 2
Roles as fishing weapons and medical value of conotoxins and conoinsulins. (A) Injection of the venom directly into the prey’s body to numb or poison it. (B) Release the venom into the surrounding water to numb the prey. (C) Diseases, receptors, and species related to different toxins and insulin. Representative cone snails are cited in the orange band. The light green band lists different targets for conotoxins or conoinsulins, including voltage-gated potassium ion channel (Kv), voltage-gated sodium channel (Nav), insulin receptor (IR), voltage-gated calcium channel (Cav), and nicotine acetylcholine receptor (nAChRs). The dark green band displays representative conotoxins or conoinsulins targeting different receptors. The blue band exemplifies typical diseases targeted by conotoxins or conoinsulins.
Figure 5
Figure 5
The phylogenetic tree of 38 different conoinsulin sequences and one insulin-like peptide from 18 species of Conus. The 39 peptide sequences were obtained from UniProt and ConoServer databases (www.uniprot.org/; http://conoserver.org/). The 39 peptide sequences were aligned using MEGA 7.0.14 software. A phylogenetic tree was established using a neighbor-Joining approach (bootstrap method 1000 and pairwise deletion 50%). The color in the inner circle of the figure indicates that insulin comes from three different dietary habits of Conus, while the color in the outer circle indicates different species of Conus.
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References

    1. Gao B., Peng C., Yang J., Yi Y., Zhang J., Shi Q. Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery. Toxins. 2017;9:397. doi: 10.3390/toxins9120397. - DOI - PMC - PubMed
    1. Himaya S.W., Jin A.H., Dutertre S., Giacomotto J., Mohialdeen H., Vetter I., Alewood P.F., Lewis R.J. Comparative Venomics Reveals the Complex Prey Capture Strategy of the Piscivorous Cone Snail Conus catus. J. Proteome Res. 2015;14:4372–4381. doi: 10.1021/acs.jproteome.5b00630. - DOI - PubMed
    1. Abalde S., Dutertre S., Zardoya R. A Combined Transcriptomics and Proteomics Approach Reveals the Differences in the Predatory and Defensive Venoms of the Molluscivorous Cone Snail Cylinder ammiralis (Caenogastropoda: Conidae) Toxins. 2021;13:642. doi: 10.3390/toxins13090642. - DOI - PMC - PubMed
    1. Prashanth J.R., Dutertre S., Jin A.H., Lavergne V., Hamilton B., Cardoso F.C., Griffin J., Venter D.J., Alewood P.F., Lewis R.J. The Role of Defensive Rcological Interactions in the Evolution of Conotoxins. Mol. Ecol. 2016;25:598–615. doi: 10.1111/mec.13504. - DOI - PubMed
    1. Lewis R.J., Dutertre S., Vetter I., Christie M.J. Conus Venom Peptide Pharmacology. Pharmacol. Rev. 2012;64:259–298. doi: 10.1124/pr.111.005322. - DOI - PubMed
-