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      Ancient Venom Systems: A Review on Cnidaria Toxins

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          Abstract

          Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.

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          Most cited references142

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          The Ctenophore Genome and the Evolutionary Origins of Neural Systems

          The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores, or comb jellies, have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here, we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well-recognized in ctenophores, many bilaterian neuron-specific genes and genes of “classical” neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.
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            Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases.

            The importance of proteinases in the pathologies associated with Viperid envenoming has long been appreciated. Over the past 40 years substantial research has clearly implicated metalloproteinases in the venom (snake venom metalloproteinases; SVMPs) as playing key roles in the development of such symptoms as hemorrhage, edema, hypotension, hypovolemia, inflammation and necrosis. In spite of this wealth of information there are still many unresolved questions pertaining to the structural basis for the various SVMPS giving rise to the diversity of activities. In this short review we will not attempt to provide an exhaustive collation of structural studies on the SVMPs; however, we will give a brief outline of the structural classification of the SVMPs; as well as relate them to the other members of the reprolysin family of metalloproteinases, the ADAMs. The information put forth in the text does not allow specific conclusions to be drawn on the structural basis for SVMP functional diversity, but it is our goal that it will allow for the development of testable hypotheses that can be experimentally pursued. What the reader will observe is that there are very interesting structural features displayed by the various SVMP classes and subclasses that provide insight into their functional characteristics.
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              Pore-forming protein toxins: from structure to function.

              Pore-forming protein toxins (PFTs) are one of Nature's most potent biological weapons. An essential feature of their toxicity is the remarkable property that PFTs can exist either in a stable water-soluble state or as an integral membrane pore. In order to convert from the water-soluble to the membrane state, the toxin must undergo large conformational changes. There are now more than a dozen PFTs for which crystal structures have been determined and the nature of the conformational changes they must undergo is beginning to be understood. Although they differ markedly in their primary, secondary, tertiary and quaternary structures, nearly all can be classified into one of two families based on the types of pores they are thought to form: alpha-PFTs or beta-PFTs. Recent work suggests a number of common features in the mechanism of membrane insertion may exist for each class.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                18 June 2015
                June 2015
                : 7
                : 6
                : 2251-2271
                Affiliations
                [1 ]Venom Evolution Lab, School of Biological Sciences, the University of Queensland, St. Lucia 4072, QLD, Australia; E-Mail: m.jouiaei@ 123456uq.edu.au
                [2 ]Institute for Molecular Bioscience, the University of Queensland, St. Lucia 4072, QLD, Australia; E-Mails: b.madio@ 123456uq.edu.au (B.M.); p.alewood@ 123456imb.uq.edu.au (P.F.A.)
                [3 ]Pacific Cnidaria Research Lab, Department of Tropical Medicine, University of Hawaii, Honolulu, HI 96822, USA; E-Mail: ayanagih@ 123456hawaii.edu
                [4 ]Department of Pathology, University of Turku, Turku FIN-20520, Finland; E-Mail: timneva@ 123456utu.fi
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: bgfry@ 123456uq.edu.au ; Tel.: +61-400-193-182.
                Article
                toxins-07-02251
                10.3390/toxins7062251
                4488701
                26094698
                9c8b107c-de8b-46ec-96cf-ff5edf8c54cd
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 May 2015
                : 10 June 2015
                Categories
                Review

                Molecular medicine
                cnidarians,venom,enzymes,pore forming toxins,neurotoxins,vasodilatory biogenic amines,human envenomation

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