Peptidomics combined with cDNA library unravel the diversity of centipede venom

Yang, Shilong; Wen, Bo; Mo, Guoxiang; Kang, Di; Liu, Jie; Lin, Zhilong; Jiang, Wenbin; Li, Bowen; Du, Chaoqin; Yang, Shuanjuan; Jiang, Hui; Qi, Feng; Xu, Xun; Wang, Jun; Lai, Ren

doi:10.1016/j.jprot.2014.10.014

Cited by 31 publications

(38 citation statements)

References 46 publications

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“…The venom peptides, which are of most interest from a drug discovery perspective, are extraordinarily diverse [25,[27][28][29][30][31][32]. Undheim et al [30] classified centipede venom peptides into 31 phylogenetically distinct families of scutigerotoxins (SCUTX1-3) and scoloptoxins ( .…”

Section: Centipede Venoms Are Complex Chemical Arsenalsmentioning

confidence: 99%

“…However, centipede HAND toxins have undergone greater radiation than those in spiders, with the HAND-form accounting for the vast majority of molecular diversity in the SLPTX3 family [29][30][31]. In centipede HAND toxins, one turn of α3 was excised to remove the residues between cysteines 4 and 5, thereby creating a highly compact and ultrastable peptide fold [21,35].…”

Section: The Slptx3 Fold: Weaponization Of a Hormonementioning

confidence: 99%

“…What was unanticipated, but perhaps should not have been given their unique venom apparatus and long evolutionary history, is that the composition of centipede venoms is vastly different to that of all other venomous animals. Only seven studies to date have probed the centipede venom proteome in detail [25,[27][28][29][30][31][32]], yet these limited investigations have uncovered 19 novel disulfide-constrained peptide families. Given the very limited taxonomic sampling of centipede venoms to date, this is likely to be the tip of the iceberg and the next decade promises to reveal more novel centipede venom peptides as additional species are examined.…”

Section: Expert Opinionmentioning

confidence: 99%

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Centipede venoms as a source of drug leads

Undheim

Jenner

King

2016

Expert Opinion on Drug Discovery

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Introduction: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure. Areas covered:This review summarizes what is currently know about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective. We also highlight the remarkable diversity of constrained threedimensional peptide scaffolds present in these venoms that might be useful for bioengineering of drug leads. Expert opinion:The resurgence of interest in peptide drugs has stimulated interest in venoms as a source of highly stable, disulfide-constrained peptides with potential as therapeutics. Well-studied venomous taxa such as cone snails and snakes have yielded FDA-approved drugs, while ancient invertebrate predators such as spiders and sea anemones have yielded molecules that are currently in preclinical studies and clinical trials, respectively. However, until recently, the paucity of research on centipede venoms made it easy to discount them as a potential source of peptides with therapeutically useful properties. Seminal studies over the past five years have revealed that centipede venoms have exceedingly complex proteomes that are perhaps richer than any other venom in unique disulfide-rich peptide scaffolds. Like most arthropod predators, centipede venoms are rich in peptides that target neuronal ion channels and receptors, but it is also becoming increasingly apparent that many of these peptides have novel or unexpected pharmacological properties with potential applications in drug discovery and development.

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Section: Centipede Venoms Are Complex Chemical Arsenalsmentioning

confidence: 99%

Section: The Slptx3 Fold: Weaponization Of a Hormonementioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

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Centipede venoms as a source of drug leads

Undheim

Jenner

King

2016

Expert Opinion on Drug Discovery

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“…They comprise approximately 3300-3500 centipede species distributed worldwide and most provinces of China (2). The body length of adult centipedes ranges from 4 to 300 mm, and venom glands are located in the first pair of limbs (3).…”

Section: Introductionmentioning

confidence: 99%

“…Complete venom peptide or protein sequences and pharmacological data are available for an even smaller number of species (9,10). Similarly, venom complexity must be further confirmed using new strategies of large-scale sequencing of broad array of centipede venoms, providing new putative proteins and enabling results to be compared among species (2,16,23). Therefore, a fully integrated approach that combines transcriptomics and peptidomics/proteomics seems essential for understanding the venom composition, venom maturation and venom production mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

Zhao

Lan

et al. 2018

Molecular & Cellular Proteomics

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SummaryCentipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twentythree and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1,369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified approximately 10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in centipede, similar to snakes.

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