Abstract
Previous studies have indicated that each conotoxin precursor has a hyperconserved signal region, a rather conserved pro region and a hypervariable mature region, and nucleotide mutations are the main driven factor. However, in this study, we made an in-depth analysis on the M-superfamily conotoxin precursors and found that the diversity of the signal, pro and mature regions are more complicated than previous findings. Different conotoxin precursors can have same signal, pro and/or mature regions, especially different conotoxin precursors with same mature region but different signal and pro regions. In addition, insertions and deletions (indels) were detected in conotoxin precursors. Indels are infrequent in the signal region but frequent in the pro and mature regions. In contrast to deletions that dominate in the pro region, insertions dominate in the mature region. The number of amino acids is crucial for the physiological functions of mature conotoxins, therefore indels, especially insertions in the mature region, play an important role in the sequence and function diversity of conotoxins.
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Barghi N, Concepcion GP, Olivera BM, Lluisma AO (2015) High conopeptide diversity in Conus tribblei revealed through analysis of venom duct transcriptome using two high-throughput sequencing platforms. Mar Biotechnol 17:81–98
Biass D, Violette A, Hulo N, Lisacek F, Favreau P, Stocklin R (2015) Uncovering intense protein diversification in a cone snail venom gland using an integrative venomics approach. J Proteome Res 14:628–638
Essack M, Bajic VB, Archer JAC (2012) Conotoxins that confer therapeutic possibilities. Mar Drugs 10:1244–1265
Figueroa-Montiel A, Ramos MA, Mares RE, Duenas S, Pimienta G, Ortiz E, Possani LD, Licea-Navarro AF (2016) In silico identification of protein disulfide isomerase gene families in the de novo assembled transcriptomes of four different species of the genus Conus. PLoS ONE 11:e0148390
Green BR, Bulaj G, Norton RS (2014) Structure and function of mu-conotoxins, peptide-based sodium channel blockers with analgesic activity. Future Med Chem 6:1677–1698
Himaya SW, Jin AH, Dutertre S, Giacomotto J, Mohialdeen H, Vetter I, Alewood PF, Lewis RJ (2015) Comparative venomics reveals the complex prey capture strategy of the piscivorous cone snail Conus catus. J Proteome Res 14:4372–4381
Jacob RB, McDougal OM (2010) The M-superfamily of conotoxins: a review. Cell Mol Life Sci: CMLS 67:17–27
Kaas Q, Westermann JC, Craik DJ (2010) Conopeptide characterization and classifications: an analysis using ConoServer. Toxicon 55:1491–1509
Kaas Q, Yu R, Jin AH, Dutertre S, Craik DJ (2012) ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Res 40:D325–D330
Kauferstein S, Melaun C, Mebs D (2005) Direct cDNA cloning of novel conopeptide precursors of the O-superfamily. Peptides 26:361–367
Lavergne V, Dutertre S, Jin AH, Lewis RJ, Taft RJ, Alewood PF (2013) Systematic interrogation of the Conus marmoreus venom duct transcriptome with ConoSorter reveals 158 novel conotoxins and 13 new gene superfamilies. BMC Genom 14:708
Lavergne V, Harliwong I, Jones A, Miller D, Taft RJ, Alewood PF (2015) Optimized deep-targeted proteotranscriptomic profiling reveals unexplored Conus toxin diversity and novel cysteine frameworks. Proc Natl Acad Sci USA 112:E3782–3791
Liu Z, Xu N, Hu J, Zhao C, Yu Z, Dai Q (2009) Identification of novel I-superfamily conopeptides from several clades of Conus species found in the South China Sea. Peptides 30:1782–1787
Lluisma AO, Milash BA, Moore B, Olivera BM, Bandyopadhyay PK (2012) Novel venom peptides from the cone snail Conus pulicarius discovered through next-generation sequencing of its venom duct transcriptome. Ma Genom 5:43–51
Nguyen B, Caer JP, Mourier G, Thai R, Lamthanh H, Servent D, Benoit E, Molgo J (2014) Characterization of a novel Conus bandanus conopeptide belonging to the M-superfamily containing bromotryptophan. Mar Drugs 12:3449–3465
Nicke A, Loughnan ML, Millard EL, Alewood PF, Adams DJ, Daly NL, Craik DJ, Lewis RJ (2003) Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence. J Biol Chem 278:3137–3144
Olivera BM (2006) Conus peptides: biodiversity-based discovery and exogenomics. J Biol Chem 281:31173–31177
Peng C, Yao G, Gao BM, Fan CX, Bian C, Wang J, Cao Y, Wen B, Zhu Y, Ruan Z, Zhao X, You X, Bai J, Li J, Lin Z, Zou S, Zhang X, Qiu Y, Chen J, Coon SL, Yang J, Chen JS, Shi Q (2016) High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing. GigaScience 5:17
Phuong MA, Mahardika GN, Alfaro ME (2016) Dietary breadth is positively correlated with venom complexity in cone snails. BMC Genom 17:401
Puillandre N, Stocklin R, Favreau P, Bianchi E, Perret F, Rivasseau A, Limpalaer L, Monnier E, Bouchet P (2014) When everything converges: integrative taxonomy with shell, DNA and venomic data reveals Conus conco, a new species of cone snails (Gastropoda: Conoidea). Mol Phylogenet Evol 80:186–192
Robinson SD, Safavi-Hemami H, McIntosh LD, Purcell AW, Norton RS, Papenfuss AT (2014) Diversity of conotoxin gene superfamilies in the venomous snail, Conus victoriae. PLoS ONE 9:e87648
Tian D, Wang Q, Zhang P, Araki H, Yang S, Kreitman M, Nagylaki T, Hudson R, Bergelson J, Chen JQ (2008) Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes. Nature 455:105–108
Wu Y, Wang L, Zhou M, You Y, Zhu X, Qiang Y, Qin M, Luo S, Ren Z, Xu A (2013) Molecular evolution and diversity of Conus peptide toxins, as revealed by gene structure and intron sequence analyses. PLoS ONE 8:e82495
Zhou M, Wang L, Wu Y, Zhu X, Feng Y, Chen Z, Li Y, Sun D, Ren Z, Xu A (2013) Characterizing the evolution and functions of the M-superfamily conotoxins. Toxicon 76:150–159
Funding
This work was funded by the National Natural Science Foundation of China (Grant Nos. 81703412 and 81402001) and Natural Science Foundation of Hunan Province (Grant Nos. 2016JJ3177 and 2018JJ3830).
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Yang, M., Zhou, M. Insertions and Deletions Play an Important Role in the Diversity of Conotoxins. Protein J 39, 190–195 (2020). https://doi.org/10.1007/s10930-020-09892-2
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DOI: https://doi.org/10.1007/s10930-020-09892-2