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Biomolecular Concepts Dec 2014Latrophilins (LPHN) are part of a yet unexplored family of receptors comprising three isoforms, LPHN1-3, and belonging to a unique branch of G protein-coupled receptors... (Review)
Review
Latrophilins (LPHN) are part of a yet unexplored family of receptors comprising three isoforms, LPHN1-3, and belonging to a unique branch of G protein-coupled receptors (GPCR) named adhesion GPCR (aGPCR). LPHN are considered to be prototypical models for the study of aGPCR as they are one of the most evolutionary conserved members. Previously described as the target for a potent neurotoxin from the black widow spider venom, LPHN are now being studied under a whole new perspective. Indeed, recent advances have provided a better understanding of different aspects of this prototypical family of receptors: 1) elucidation of LPHN ectodomain organization by crystallography has unveiled a new functional domain with great repercussion on all the other members of the aGPCR family, 2) proteomic approaches have opened the gate to unsuspected functional characteristics of LPHN cellular role, and 3) genetic approaches have provided hints into the physiological functions of LPHN in specific systems and organisms. Moreover, genomic linkage studies screening human patients from diverse genetic backgrounds have involved LPHN gene defects in human disorders such as attention-deficit hyperactivity disorder and cancer. In this review, we will provide a historical perspective addressing experimental research on these receptors while highlighting the new advances and discoveries concerning LPHN functions. As GPCR still represent the most studied targets for the development of pharmacological approaches aiming at alleviating human disorders, the relevance of studying LPHN retains a high pertinence to better understand these receptors for the treatment of human diseases.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Gene Expression Regulation, Developmental; Humans; Neoplasms; Organ Specificity; Phosphorylation; Protein Structure, Tertiary; Receptors, G-Protein-Coupled; Receptors, Peptide; Spider Venoms; Synapses; Terminology as Topic
PubMed: 25429599
DOI: 10.1515/bmc-2014-0032 -
Toxins Aug 2021Arthropod venoms offer a promising resource for the discovery of novel bioactive peptides and proteins, but the limited size of most species translates into minuscule...
Arthropod venoms offer a promising resource for the discovery of novel bioactive peptides and proteins, but the limited size of most species translates into minuscule venom yields. Bioactivity studies based on traditional fractionation are therefore challenging, so alternative strategies are needed. Cell-free synthesis based on synthetic gene fragments is one of the most promising emerging technologies, theoretically allowing the rapid, laboratory-scale production of specific venom components, but this approach has yet to be applied in venom biodiscovery. Here, we tested the ability of three commercially available cell-free protein expression systems to produce venom components from small arthropods, using U-sicaritoxin-Sdo1a from the six-eyed sand spider as a case study. We found that only one of the systems was able to produce an active product in low amounts, as demonstrated by SDS-PAGE, mass spectrometry, and bioactivity screening on murine neuroblasts. We discuss our findings in relation to the promises and limitations of cell-free synthesis for venom biodiscovery programs in smaller invertebrates.
Topics: Biotechnology; Cell-Free System; Protein Biosynthesis; Spider Venoms; Synthetic Biology
PubMed: 34437446
DOI: 10.3390/toxins13080575 -
Molecules (Basel, Switzerland) Dec 2023Spiders (Araneae), having thrived for over 300 million years, exhibit remarkable diversity, with 47,000 described species and an estimated 150,000 species in existence.... (Review)
Review
Spiders (Araneae), having thrived for over 300 million years, exhibit remarkable diversity, with 47,000 described species and an estimated 150,000 species in existence. Evolving with intricate venom, spiders are nature's skilled predators. While only a small fraction of spiders pose a threat to humans, their venoms contain complex compounds, holding promise as drug leads. Spider venoms primarily serve to immobilize prey, achieved through neurotoxins targeting ion channels. Peptides constitute a major part of these venoms, displaying diverse pharmacological activities, and making them appealing for drug development. Moreover, spider-venom peptides have emerged as valuable tools for exploring human disease mechanisms. This review focuses on the roles of spider-venom peptides in spider survival strategies and their dual significance as pharmaceutical research tools. By integrating recent discoveries, it provides a comprehensive overview of these peptides, their targets, bioactivities, and their relevance in spider survival and medical research.
Topics: Humans; Biomedical Research; Drug Development; Neurotoxins; Peptides; Spider Venoms
PubMed: 38202621
DOI: 10.3390/molecules29010035 -
Toxins Oct 2019This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis.... (Review)
Review
This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis. Major venom component groups are small molecular mass compounds, antimicrobial (also called cytolytic, or cationic) peptides (only in some spider families), cysteine-rich (neurotoxic) peptides, and enzymes and proteins. Cysteine-rich peptides are reviewed with respect to various structural motifs, their targets (ion channels, membrane receptors), nomenclature, and molecular binding. We further describe the latest findings concerning the maturation of antimicrobial, and cysteine-rich peptides that are in most known cases expressed as propeptide-containing precursors. Today, venom research, increasingly employs transcriptomic and mass spectrometric techniques. Pros and cons of venom gland transcriptome analysis with Sanger, 454, and Illumina sequencing are discussed and an overview on so far published transcriptome studies is given. In this respect, we also discuss the only recently described cross contamination arising from multiplexing in Illumina sequencing and its possible impacts on venom studies. High throughput mass spectrometric analysis of venom proteomes (bottom-up, top-down) are reviewed.
Topics: Animals; Gene Expression Profiling; Humans; Proteomics; Spider Venoms
PubMed: 31652611
DOI: 10.3390/toxins11100611 -
Toxins Mar 2012Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world's annual crop... (Review)
Review
Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world's annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics) and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides.
Topics: Animals; Humans; Insecticides; Peptides; Protein Conformation; Spider Venoms
PubMed: 22741062
DOI: 10.3390/toxins4030191 -
Toxins Dec 2010Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious... (Review)
Review
Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.
Topics: Analgesics; Animals; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antifungal Agents; Antimalarials; Cystine Knot Motifs; Erectile Dysfunction; Humans; Male; Peptides; Spider Venoms
PubMed: 22069579
DOI: 10.3390/toxins2122851 -
Scientific Data Nov 2023The Tibellus oblongus spider is an active hunter that does not spin webs and remains highly underinvestigated in terms of the venom composition. Here, we describe venom...
The Tibellus oblongus spider is an active hunter that does not spin webs and remains highly underinvestigated in terms of the venom composition. Here, we describe venom glands transcriptome and venom proteome analysis for unveiling the polypeptide composition of Tibellus oblongus spider venom. The resulting EST database includes 1733 records, including 1263 nucleotide sequences with ORFs, of these 942 have been identified as toxin-coding. The database of peptide sequences was built based on of the transcriptomics results. It contains 217 new toxins, 212 of them were detected in the T. oblongus venom by the proteomics.
Topics: Amino Acid Sequence; Gene Expression Profiling; Proteomics; Spider Venoms; Transcriptome; Venoms; Animals
PubMed: 37993463
DOI: 10.1038/s41597-023-02703-0 -
Toxins Jul 2016Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis,... (Review)
Review
Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis, paralysis, and excruciating pain. Information on venom composition and the toxins present in these species is growing due to an interest in using bioactive toxins from spiders and scorpions for drug discovery purposes and for solving crystal structures of membrane-embedded receptors. Additionally, the identification and isolation of a myriad of spider and scorpion toxins has allowed research within next generation antivenoms to progress at an increasingly faster pace. In this review, the current knowledge of spider and scorpion venoms is presented, followed by a discussion of all published biotechnological efforts within development of spider and scorpion antitoxins based on small molecules, antibodies and fragments thereof, and next generation immunization strategies. The increasing number of discovery and development efforts within this field may point towards an upcoming transition from serum-based antivenoms towards therapeutic solutions based on modern biotechnology.
Topics: Animals; Antivenins; Biotechnology; Computational Biology; Databases, Protein; Drug Discovery; Humans; Scorpion Stings; Scorpion Venoms; Spider Bites; Spider Venoms
PubMed: 27455327
DOI: 10.3390/toxins8080226 -
Toxins Nov 2018Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated... (Review)
Review
Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.
Topics: Animals; Antivenins; Humans; Snake Bites; Snake Venoms; Spider Bites; Spider Venoms
PubMed: 30400220
DOI: 10.3390/toxins10110452 -
Toxins Jun 2019Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic... (Review)
Review
Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic manifestations such as renal failure and hematological disturbances. Several toxins make up the venom of these species, and they are mainly peptides and proteins ranging from 5-40 kDa. The venoms have three major families of toxins: phospholipases-D, astacin-like metalloproteases, and the inhibitor cystine knot (ICK) peptides. Serine proteases, serpins, hyaluronidases, venom allergens, and a translationally controlled tumor protein (TCTP) are also present. Toxins hold essential biological properties that enable interactions with a range of distinct molecular targets. Therefore, the application of toxins as research tools and clinical products motivates repurposing their uses of interest. This review aims to discuss possibilities for brown spider venom toxins as putative models for designing molecules likely for therapeutics based on the status quo of brown spider venoms. Herein, we explore new possibilities for the venom components in the context of their biochemical and biological features, likewise their cellular targets, three-dimensional structures, and mechanisms of action.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Humans; Immunotherapy; Insecticides; Neuroprotective Agents; Peptides; Phosphoric Diester Hydrolases; Recombinant Proteins; Serine Proteinase Inhibitors; Spider Venoms; Tumor Protein, Translationally-Controlled 1
PubMed: 31248109
DOI: 10.3390/toxins11060355