Analysis of NGS data from Peruvian Loxosceles laeta spider venom gland reveals toxin diversity

Medina-Santos, Raíssa; Costa, Tamara G.F.; Assis, Thamyres C.S. de; Kalapothakis, Yan; Lima, Sergio Monteiro; Carmo, Anderson Oliveira do; Gonzalez-Kozlova, Edgar E.; Kalapothakis, Evanguedes; Chávez-Olortégui, Carlos; Guerra-Duarte, Clara

doi:10.1016/j.cbd.2022.101017

Cited by 3 publications

(4 citation statements)

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“…Previous studies have attempted to correlate the biochemical and biophysical properties of venom proteins with their in vitro activities [4,15]. Transcriptomes of Loxosceles venom glands [29][30][31][32] and proteomes of venoms [33][34][35] have identified numerous proteins with varied toxic actions upon different species. The PLDs are particularly interesting since they reproduce in vitro several manifestations of loxoscelism, such as dermonecrosis, with the presence of abundant inflammatory polymorphonuclear cells and a prominent edema.…”

Section: Discussionmentioning

confidence: 99%

“…Understanding the underlying molecular and cell signaling pathways triggered by these enzymes, particularly those implicated in uncontrolled inflammatory response is of relevance [23,25,[36][37][38][39][40]. Comparative analyses of transcripts from the venom glands of different brown spider species identified the variations in toxin contents for the Brazilian L. laeta [29], Peruvian L. laeta [32], L. similis [31], and L. intermedia [30]. Venom proteome analyses of L. gaucho [34] and L. intermedia [33,35] also demonstrated the existence of differences in the toxin profiles.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three Loxosceles Spider Venoms

da Justa,

Hernández González,

Vuitika

et al. 2023

IJMS

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Spiders of Loxosceles genus are widely distributed and their venoms contain phospholipases D (PLDs), which degrade phospholipids and trigger inflammatory responses, dermonecrosis, hematological changes, and renal injuries. Biochemical, functional, and structural properties of three recombinant PLDs from L. intermedia, L. laeta, and L. gaucho, the principal species clinically relevant in South America, were analyzed. Sera against L. gaucho and L. laeta PLDs strongly cross-reacted with other PLDs, but sera against L. intermedia PLD mostly reacted with homologous molecules, suggesting underlying structural and functional differences. PLDs presented a similar secondary structure profile but distinct melting temperatures. Different methods demonstrated that all PLDs cleave sphingomyelin and lysophosphatidylcholine, but L. gaucho and L. laeta PLDs excelled. L. gaucho PLD showed greater “in vitro” hemolytic activity. L. gaucho and L. laeta PLDs were more lethal in assays with mice and crickets. Molecular dynamics simulations correlated their biochemical activities with differences in sequences and conformations of specific surface loops, which play roles in protein stability and in modulating interactions with the membrane. Despite the high similarity, PLDs from L. gaucho and L. laeta venoms are more active than L. intermedia PLD, requiring special attention from physicians when these two species prevail in endemic regions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three Loxosceles Spider Venoms

da Justa,

Hernández González,

Vuitika

et al. 2023

IJMS

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“…In minor cases, systemic manifestations, including renal failure and hematological disturbances, such as intravascular hemolysis and hemolytic anemia, have been observed [ 4 , 5 , 6 ]. Based on proteome and transcriptome analyses, brown spider venoms mainly comprise low-molecular-mass proteins and peptides, principally in the 5–40 kDa range [ 7 , 8 , 9 , 10 ]. There are three classes of “highly expressed molecules” that make up approximately 95% of the toxin-encoding transcripts in the venom gland: phospholipases-D (PLD), astacin-like proteases, and low molecular mass peptides biochemically characterized as Knottins [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Based on proteome and transcriptome analyses, brown spider venoms mainly comprise low-molecular-mass proteins and peptides, principally in the 5–40 kDa range [ 7 , 8 , 9 , 10 ]. There are three classes of “highly expressed molecules” that make up approximately 95% of the toxin-encoding transcripts in the venom gland: phospholipases-D (PLD), astacin-like proteases, and low molecular mass peptides biochemically characterized as Knottins [ 7 , 8 , 9 , 10 ]. The study of venom compositions from brown spiders indicates that the PLD toxin family is the principal protein responsible for the clinical symptoms observed in Loxoscelism victims [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates

Chaves-Moreira

Gremski

Moraes

et al. 2023

Toxins

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Brown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme’s substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.

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Transformation-associated recombination (TAR) cloning and its applications for gene function; genome architecture and evolution; biotechnology and biomedicine

Kouprina,

Larionov

2023

Oncotarget

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Transformation-associated recombination (TAR) cloning represents a unique tool to selectively and efficiently recover a given chromosomal segment up to several hundred kb in length from complex genomes (such as animals and plants) and simple genomes (such as bacteria and viruses). The technique exploits a high level of homologous recombination in the yeast Sacharomyces cerevisiae . In this review, we summarize multiple applications of the pioneering TAR cloning technique, developed previously for complex genomes, for functional, evolutionary, and structural studies, and extended the modified TAR versions to isolate biosynthetic gene clusters (BGCs) from microbes, which are the major source of pharmacological agents and industrial compounds, and to engineer synthetic viruses with novel properties to design a new generation of vaccines. TAR cloning was adapted as a reliable method for the assembly of synthetic microbe genomes for fundamental research. In this review, we also discuss how the TAR cloning in combination with HAC (human artificial chromosome)- and CRISPR-based technologies may contribute to the future.

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Analysis of NGS data from Peruvian Loxosceles laeta spider venom gland reveals toxin diversity

Cited by 3 publications

References 59 publications

Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three Loxosceles Spider Venoms

Comparative Biochemical, Structural, and Functional Analysis of Recombinant Phospholipases D from Three Loxosceles Spider Venoms

Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates

Transformation-associated recombination (TAR) cloning and its applications for gene function; genome architecture and evolution; biotechnology and biomedicine

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