venom gland
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2022 ◽  
Author(s):  
Ksenia G Kuznetsova ◽  
Sofia S Zvonareva ◽  
Rustam Ziganshin ◽  
Elena S Mekhova ◽  
Polina Yu Dgebuadze ◽  
...  

Venoms of predatory marine cone snails (the family Conidae, order Neogastropoda) are intensely studied because of the broad range of biomedical applications of the neuropeptides that they contain, conotoxins. Meanwhile anatomy in some other neogastropod lineages strongly suggests that they have evolved similar venoms independently of cone snails, nevertheless their venom composition remains unstudied. Here we focus on the most diversified of these lineages, the genus Vexillum (the family Costellariidae). We have generated comprehensive multi-specimen, multi-tissue RNA-Seq data sets for three Vexillum species, and supported our findings in two species by proteomic profiling. We show that venoms of Vexillum are dominated by highly diversified short cysteine-rich peptides that in many aspects are very similar to conotoxins. Vexitoxins possess the same precursor organization, display overlapping cysteine frameworks and share several common post-translational modifications with conotoxins. Some vexitoxins show detectable sequence similarity to conotoxins, and are predicted to adopt similar domain conformations, including a pharmacologically relevant inhibitory cysteine-know motif (ICK). The tubular gL of Vexillum is a notably more recent evolutionary novelty than the conoidean venom gland. Thus, we hypothesize lower divergence between the toxin genes, and their somatic counterparts compared to that in conotoxins, and we find support for this hypothesis in the molecular evolution of the vexitoxin cluster V027. We use this example to discuss how future studies on vexitoxins can inform origin and evolution of conotoxins, and how they may help addressing standing questions in venom evolution.


BMC Biology ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Bing Xie ◽  
Daniel Dashevsky ◽  
Darin Rokyta ◽  
Parviz Ghezellou ◽  
Behzad Fathinia ◽  
...  

Abstract Background The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom or mucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Results Transcriptomes were constructed for the following families and species: Colubridae - Helicops leopardinus, Heterodon nasicus, Rhabdophis subminiatus; Homalopsidae – Homalopsis buccata; Lamprophiidae - Malpolon monspessulanus, Psammophis schokari, Psammophis subtaeniatus, Rhamphiophis oxyrhynchus; and Viperidae – Bitis atropos, Pseudocerastes urarachnoides, Tropidolaeumus subannulatus, Vipera transcaucasiana. These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP/BNP tailed condition. Also shown was that the de novo evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances in procoagulant venoms where kunitz peptides were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within Bungarus venoms. Conclusions We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator–prey evolutionary arms races, ascertain differential clinical pathologies, as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline.


2022 ◽  
Vol 119 (1) ◽  
pp. e2111392119
Author(s):  
Giulia Zancolli ◽  
Maarten Reijnders ◽  
Robert M. Waterhouse ◽  
Marc Robinson-Rechavi

Animals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a mixture of potent bioactive molecules to subdue prey or predators—venom. This makes it one of the most widespread, convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed a comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland–specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turn, activates regulatory networks for epithelial development, cell turnover, and maintenance, which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents a first step toward an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom.


2022 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Javad Khodayar ◽  
Masoud Mahdavinia ◽  
Masoumeh Baradaran ◽  
Amir Jalali

Background: Scorpions and other venomous animals are sought with great concern because venom is a source of novel peptides with exciting features. Some toxins of scorpion venom are effectors of potassium channels. Previous studies strongly support the importance of potassium channel toxins for use as pharmacological tools or potential drugs. Objectives: Here, a three-dimensional (3-D) structure and function of a potent acidic blocker of the human voltage-gated potassium ion channel, Kv1.3, previously identified in the scorpion Mesobuthus eupeus venom gland, were interpreted. Methods: The 3-D structure of meuK2-2 was generated using homology modeling. The interaction of meuK2-2 with the Kv1.3 channel was evaluated using a computational protocol employing peptide-protein docking experiments, pose clustering, and 100 ns molecular dynamic simulations to make the 3-D models of the meuK2-2/Kv1.3 complex trustworthy. Results: A CSα/β (cysteine-stabilized α-helical and β-sheet) fold was found for the 3-D structure of meuK2-2. In a different mechanism from what was identified so far, meuK2-2 binds to both turret and pore loop of Kv1.3 through two key residues (Ala28 and Ser11) and H-bonds. The binding of meuK2-2 induces some conformational changes to Kv1.3. Eventually, the side chain of a positively charged amino acid (His9) occupies the channel's pore. All together blocks the ion permeation pathway. Conclusions: MeuK2-2 could block Kv1.3 by a new mechanism. So, it could be a unique target for further investigations to develop a pharmacological tool and potential drug.


BIOCELL ◽  
2022 ◽  
Vol 46 (3) ◽  
pp. 821-828
Author(s):  
LIMIN CHEN ◽  
XIAOWEI LI ◽  
TIANJUN HE ◽  
QUANCONG WU ◽  
TINGTING CHEN ◽  
...  

BIOCELL ◽  
2022 ◽  
Vol 46 (3) ◽  
pp. 821-828
Author(s):  
LIMIN CHEN ◽  
XIAOWEI LI ◽  
TIANJUN HE ◽  
QUANCONG WU ◽  
TINGTING CHEN ◽  
...  

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 47
Author(s):  
Pornsawan Khamtorn ◽  
Steve Peigneur ◽  
Fernanda Gobbi Amorim ◽  
Loïc Quinton ◽  
Jan Tytgat ◽  
...  

The brown widow spider, Latrodectus geometricus, is a predator of a variety of agricultural insects and is also hazardous for humans. Its venom is a true pharmacopeia representing neurotoxic peptides targeting the ion channels and/or receptors of both vertebrates and invertebrates. The lack of transcriptomic information, however, limits our knowledge of the diversity of components present in its venom. The purpose of this study was two-fold: (1) carry out a transcriptomic analysis of the venom, and (2) investigate the bioactivity of the venom using an electrophysiological bioassay. From 32,505 assembled transcripts, 8 toxin families were classified, and the ankyrin repeats (ANK), agatoxin, centipede toxin, ctenitoxin, lycotoxin, scorpion toxin-like, and SCP families were reported in the L. geometricus venom gland. The diversity of L. geometricus venom was also uncovered by the transcriptomics approach with the presence of defensins, chitinases, translationally controlled tumor proteins (TCTPs), leucine-rich proteins, serine proteases, and other important venom components. The venom was also chromatographically purified, and the activity contained in the fractions was investigated using an electrophysiological bioassay with the use of a voltage clamp on ion channels in order to find if the neurotoxic effects of the spider venom could be linked to a particular molecular target. The findings show that U24-ctenitoxin-Pn1a involves the inhibition of the insect sodium (Nav) channels, BgNav and DmNav. This study provides an overview of the molecular diversity of L. geometricus venom, which can be used as a reference for the venom of other spider species. The venom composition profile also increases our knowledge for the development of novel insecticides targeting voltage-gated sodium channels.


2021 ◽  
Author(s):  
Li jun Ding ◽  
Xiu mei Wu ◽  
Cheng gui Zhang ◽  
Peng fei Gao ◽  
Yan Zhang ◽  
...  

Abstract Natural molecules from spider venom are considered potential drugs for diseases including cancer and pain, as well as the development of new biological insecticides for agricultural use. During coevolution in the long-term predator-prey game, spiders have formed a huge molecular diversity of toxins. As of March 1 of 2021, a total of 49,243 spider species had been described, but studies of venom have been performed in only a few hundred of these species due to the difficulty of collecting venom. Two technologies have helped partially dealing with this limitation in the recent past: the screening of cDNA libraries constructed from venom gland mRNAs and the heterologous expression of the coded peptides for functional characterization. In this study, transcriptomic analysis was performed to describe the predicted toxins of Sinopoda pengi (hereafter S. pengi) and Trichonephila clavata (hereafter T. clavata). The Trinity assembly result in 163,418 transcripts, 114,127 unigene of S. pengi and 125,099 transcripts, 87,084 unigene of T. clavata. A total of 22 and 24 unigenes were identified which were predicted to inhibitor cysteine knot (ICK) toxins from S. pengi and T. clavata, respectively. In summary, molecular templates with potential application value in medical and biological fields were obtained by classifying and characterizing presumed venom components, which lays a foundation for the further study of venom.


Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 858
Author(s):  
Lhiri Hanna De Lucca Caetano ◽  
Milton Yutaka Nishiyama-Jr ◽  
Bianca de Carvalho Lins Fernandes Távora ◽  
Ursula Castro de Oliveira ◽  
Inácio de Loiola Meirelles Junqueira-de-Azevedo ◽  
...  

Among the Chilopoda class of centipede, the Cryptops genus is one of the most associated with envenomation in humans in the metropolitan region of the state of São Paulo. To date, there is no study in the literature about the toxins present in its venom. Thus, in this work, a transcriptomic characterization of the Cryptops iheringi venom gland, as well as a proteomic analysis of its venom, were performed to obtain a toxin profile of this species. These methods indicated that 57.9% of the sequences showed to be putative toxins unknown in public databases; among them, we pointed out a novel putative toxin named Cryptoxin-1. The recombinant form of this new toxin was able to promote edema in mice footpads with massive neutrophils infiltration, linking this toxin to envenomation symptoms observed in accidents with humans. Our findings may elucidate the role of this toxin in the venom, as well as the possibility to explore other proteins found in this work.


Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 828
Author(s):  
Aimee Bowman ◽  
Chloe Fitzgerald ◽  
Jeff F. Pummill ◽  
Douglas D. Rhoads ◽  
Tsunemi Yamashita

Body tissue and venom glands from an eastern population of the scorpion Centruroides vittatus (Say, 1821) were homogenized and molecular constituents removed to characterize putative sodium β toxin gene diversity, RT-qPCR, transcriptomic, and proteomic variation. We cloned sodium β toxins from genomic DNA, conducted RT-qPCR experiments with seven sodium β toxin variants, performed venom gland tissue RNA-seq, and isolated venom proteins for mass spectrophotometry. We identified >70 putative novel sodium β toxin genes, 111 toxin gene transcripts, 24 different toxin proteins, and quantified sodium β toxin gene expression variation among individuals and between sexes. Our analyses contribute to the growing evidence that venom toxicity among scorpion taxa and their populations may be associated with toxin gene diversity, specific toxin transcripts variation, and subsequent protein production. Here, slight transcript variation among toxin gene variants may contribute to the major toxin protein variation in individual scorpion venom composition.


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