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Background We successfully captured a kind of gelatinous organism DA-6 from Antarctic water, extracted its total RNAs and proteins, and performed species identification through a combination of transcriptomics and proteomics in this study. Methods The gelatinous organism DA-6 was captured 200 m underwater in Antarctica. Total RNA was extracted to construct the transcriptome and the proteins were identified by LC-MS/MS. Results DA-6 was identified as an Antarctic Salpa sp. through morphological examination and MT-CO1 phylogenetic analysis. A total of 47,183 unigenes were harvested through transcriptome. We also successfully annotated 11,954 (25.34%), 10,006 (22.21%), 4469 (9.47%) and 4901 (9.71%) unigenes with NR, SwissProt, GO and KEGG databases, respectively. In the proteomic analysis, a total of 4680 peptides and 1280 proteins were harvested using the transcriptome as the reference database. A number of both 549 (31.98%) proteins reannotated against the GO and KEGG databases. Moreover, a number of 5 toxic proteins matched from the 89 toxin-related unigenes were successfully screened, including 2 metalloproteinases, 1 serine protease, 1 serine protease inhibitor and 1 aflatoxin. Conclusion Our study is the first to identify an Antarctic Salpa sp. according to the combination of de novo transcriptomics and proteomics, which can further be served as a public database for the identification of potential polar Salpa-derived lead compounds. In addition to morphology and CO1, the combined analysis of transcriptome and proteome can also be used as a value method for new species identify e.g. Salpa sp.

Traditional Chinese medicine (TCM) has become a crucial cause of drug-induced liver injury (DILI). Differ from chemical medicines, TCM feature more complex and mostly indefinite components. This review aimed to clarify the classification, underlying mechanisms and targets of the risk components in TCM-induced liver injury to further guide the secure application of TCM. Relevant studies or articles published on the PubMed database from January 2008 to December 2019 were searched. Based on the different chemical structures of the risk ingredients in TCM, they are divided into alkaloids, glycosides, toxic proteins, terpenoids and lactones, anthraquinones, and heavy metals. According to whether drug metabolism is activated or hepatocytes are directly attacked during TCM-induced liver injury, the high-risk substances can be classified into metabolic activation, non-metabolic activation, and mixed types. Mechanisms of the hepatotoxic ingredients in TCM-induced hepatotoxicity, including cytochrome P450 (CYP450) induction, mitochondrial dysfunction, oxidative damage, apoptosis, and idiosyncratic reaction, were also summarized. The targets involved in the risk ingredient-induced hepatocellular injury mainly include metabolic enzymes, nuclear receptors, transporters, and signaling pathways. Our periodic review and summary on the risk signals of TCM-induced liver injury must be beneficial to the integrated analysis on the multi-component, multi-target, and multi-effect characteristics of TCM-induced hepatotoxicity.

Protein aggregates result from altered structural conformations and they can perturb cellular homeostasis. Prevention mechanisms, which function against protein aggregation by modulatory processes, are diverse and redundant. In this study, we have characterized Huntingtin interacting protein K (HYPK) as a global aggregation-regulatory protein. We report the mechanistic details of how HYPK's aggregation-prone regions allow it to sense and prevent other toxic protein's aggregation by forming unique annular-shaped sequestration complexes. Screenings for interacting partners of different aggregation-prone proteins identify HYPK as a global interacting partner/regulator of Huntingtin97Qexon1, α-Synuclein-A53T and Superoxide dismutase1-G93A. C-terminal hydrophobic region in HYPK makes direct contacts with aggregates to initiate the formation of sequestration complexes. HYPK acts as aggregate sensor by existing in a seeded amyloid-like state which also favors its own concentration-dependent self-oligomerization. Oligomerization of HYPK leads to annular and non-fibrillar/amorphous aggregates. Two hydrophobic segments in the C-terminus of HYPK are responsible for its own aggregations. Self-association of HYPK follows seed nucleation, in which oligomeric HYPK seeds nucleate to annular structures. Annular oligomers of HYPK fuse with each other to form amorphous aggregates. HYPK shows differential interactions with aggregation-prone and non-aggregating proteins, as it preferentially binds to aggregation-prone proteins with higher affinity than native/non-aggregating proteins. This favors the formation of HYPK's sequestration complexes both in cytosol and in ribosome. Besides having aggregation-preventive property, HYPK also reduces the cellular level of toxic proteins. In vivo, HYPK sequestration complexes prevent the formation of toxic protein aggregates to physiologically show positive impact on cell survival and restoration of normal cell physiology.

Botulinum neurotoxins (BoNTs) are the most toxic proteins in nature. Endopeptidase-mass-spectrometry (Endopep-MS) is used as a specific and rapid in-vitro assay to detect BoNTs. In this assay, immunocaptured toxin cleaves a serotype-specific-peptide-substrate, and the cleavage products are then detected by MS. Here we describe the design of a new peptide substrate for improved detection of BoNT type A (BoNT/A). Our strategy was based on reported BoNT/A-SNAP-25 interactions integrated with analysis method efficiency considerations. Integration of the newly designed substrate led to a 10-fold increase in the assay sensitivity both in buffer and in clinically relevant samples.

Neurodegenerative diseases are closely associated with the amplification and invasion of toxic proteins. In particular Alzheimer's disease is characterized by the systematic progression of amyloid-$\beta$ and $\tau$-proteins in the brain. These two protein families are coupled and it is believed that their joint presence greatly enhances the resulting damage. Here, we examine a class of coupled chemical kinetics models of healthy and toxic proteins in two spatial dimensions. The anisotropic diffusion expected to take place within the brain along axonal pathways is factored in the models and produces a filamentary, predominantly one-dimensional transmission. Nevertheless, the potential of the anisotropic models towards generating interactions taking advantage of the two-dimensional landscape is showcased. Finally, a reduction of the models into a simpler family of generalized Fisher-Kolmogorov-Petrovskii-Piskunov (FKPP) type systems is examined. It is seen that the latter captures well the qualitative propagation features, although it may somewhat underestimate the concentrations of the toxic proteins., Comment: 11 pages, 8 figures

Ribosome-associated Quality Control (RQC) pathways protect cells from toxicity caused by incomplete protein products resulting from translation of damaged or problematic mRNAs. Extensive work in yeast has identified highly conserved mechanisms that lead to the degradation of the faulty mRNA and partially synthesized polypeptide. Here, we used CRISPR-Cas9-based screening to search for additional RQC strategies in mammals. We found that failed translation leads to specific inhibition of translation initiation on that message. This negative feedback loop is mediated by two translation inhibitors, GIGYF2 and 4EHP. Both model substrates and growth-based assays established that inhibition of additional rounds of translation acts in concert with known RQC pathways to prevent buildup of toxic proteins. Inability to block translation of faulty mRNAs, and subsequent accumulation of partially synthesized polypeptides, could explain the neurodevelopmental and neuropsychiatric disorders observed in mice and humans with compromised GIGYF2 function.

Ricin, abrin and related plant toxins have played interesting and important roles in the history of clinical medicine and biomedical research. The use of these proteins in medical treatment since ancient times is reviewed. Later the proteins played important roles in the early days of immunological research and some of the fundamental principles of immunology were discovered with toxic proteins of this group. During the last three decades the mechanism of action of the toxins was elucidated. This led to a major effort to target the toxins to malignant cells. Ricin has been used in bioterrorism. Recently, the toxins have played important roles as experimental models to elucidate the intracellular trafficking of endocytosed proteins.

The pharmacological potential of sea anemone toxins has prompted the improvement of the biochemical and structural knowledge of such toxic proteins. Cangitoxin (CGX) is a new sea anemone toxin found in Bunudosoma cangicum . Long range molecular dynamics in vacuum and also with an explicit solvent representation was used to generate a structural model of CGX. The main structural features, three S–S bridges and anti-parallel β-sheet strands that characterize all known sea anemone toxins, are observed in the final CGX model. The structural analysis of CGX clearly suggests this protein just like a type-I sea anemone toxin. Additionally, the presence of an intensive positive electrostatic field related to positive residues at the vicinity of position 35 and a salt bridge configuration obtained for the Arg14 containing-loop could be directly involved in tissue discrimination and binding affinity of CGX to the Na + channel receptor.

Toxic proteins are produced by a diversity of venomous animals from various phyla. They are often of small size, possess a large density of disulfide bonds and exert multiple functions directed toward a variety of molecular targets, including a diversity of enzymes and ion channels. The aim of this brief and non-exhaustive review is three-fold. First, the structural context associated with the functional diversity of animal toxins is presented. Among various situations, it is shown that toxins with a similar fold can exert different functions and that toxins with unrelated folds can exert similar functions. Second, the functional sites of some animal toxins are presented. Their comparison shed light on how (i) distinct functions can be exerted by similarly folded toxins and (ii) similar functions can be shared by structurally distinct toxins. Third, it is shown that part of the functional site of foreign proteins can be grafted on an animal toxin scaffold, opening new perspectives in the domain of protein engineering.

Characteristic representatives of the hypersuperfamily comprising digestive enzymes, hormones and a large series of toxins as well as the nodal ancestor of trypsin-related serine proteases and proinsulin have been compared with six unusual (not clearly related) toxins from organisms representing different levels of evolutionary development. In the course of comparison a modification of the previously suggested optimum variant approach is used, making it possible to compare groups of distantly related proteins. A clearly expressed periodicity of the same type is observed in the unusual toxins. The relationship of all proteins examined is established, giving the evolutionary order: serine proteases → proinsulin → toxic proteins.

A large number of sequences of digestive enzymes, hormones and a large series of toxins from organisms representing different levels of evolutionary development have been compared and the results juxtaposed with data about their functions and active sites. This allows random coincidences to be excluded; they serve as a background, against which the real albeit weak analogies are outlined. The results show proinsulin as a protein closest to the common ancestor of the proteins compared. Next in this respect are ribonuclease and phospholipase. It is established that most of the examined proteins are related and constitute a superfamily of a higher level—hypersuperfamily. Evidence in favour of the evolutionary order: cardiotoxins→short and long snake neurotoxins is also presented.

The deoiled meal of tung (Aleurites fordii Hemsl.) kernels is usually a waste because of its toxic effects on livestock, while its oil has some industrial uses. The defatted material was tested for the quantitative levels of common antinutritional factors like tannins and saponins which were found to be 1·55 and 0·72% respectively. The material was tested for detoxification by giving double treatment of rectified spirit followed by 0·2 M sodium hydroxide for a duration of 24 h each. The treated material (containing residual tannins 0·15% and saponins 0·26%) was then tested on one-week-old hybrid male chicks by feeding at 5 and 10% levels for a period of six weeks. The depression in the growth rates was significantly low (P ≤ 0·05) at 10% level of its feeding, while at its 5% level, the growth depression was non-significant. The overall retarded growth syndrome due to this material may be a result of overall affliction of the body metabolism of the experimental chicks, due to the toxic proteins which this material is reported to contain.