CDD: a Conserved Domain Database for the functional annotation of proteins

Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where they orchestrate a parasitic existence. Herein we provide the first comprehensive characterization of the excretory/secretory products of T. muris. We identify 148 proteins secreted by T. muris and show for the first time that the mouse whipworm secretes exosome-like extracellular vesicles (EVs) that can interact with host cells. We use an Optiprep® gradient to purify the EVs, highlighting the suitability of this method for purifying EVs secreted by a parasitic nematode. We also characterize the proteomic and genomic content of the EVs, identifying >350 proteins, 56 miRNAs (22 novel) and 475 full-length mRNA transcripts mapping to T. muris gene models. Many of the miRNAs putatively mapped to mouse genes are involved in regulation of inflammation, implying a role in parasite-driven immunomodulation. In addition, for the first time to our knowledge, colonic organoids have been used to demonstrate the internalization of parasite EVs by host cells. Understanding how parasites interact with their host is crucial to develop new control measures. This first characterization of the proteins and EVs secreted by T. muris provides important information on whipworm–host communication and forms the basis for future studies.

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“…Putative signal peptides and transmembrane domain(s) were predicted using the programs CD-Search tool [29] and SignalP [30]. …”

Section: Methodsmentioning

confidence: 99%

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

Eichenberger

Talukder

Field

et al. 2018

J of Extracellular Vesicle

112

145

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“…Eight of these 17 proteins were very similar to existing proteins, with one (IP βII-C -7) identical to “THAP domain containing, apoptosis associated protein 3, isoform CRA g”. Each member of the THAP family consists of a conserved domain [34], the THAP domain, which is a putative DNA-binding domain and probably also binds a zinc ion. This is a novel protein motif with similarity to the DNA-binding domain of P element transposase in Drosophila [35].…”

Section: Discussionmentioning

confidence: 99%

Non-erythroid beta spectrin interacting proteins and their effects on spectrin tetramerization

Sevinc

Fung

2011

Cellular and Molecular Biology Letters

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With yeast two-hybrid methods, we used a C-terminal fragment (residues 1697-2145) of non-erythroid beta spectrin (βII-C), including the region involved in the association with alpha spectrin to form tetramers, as the bait to screen a human brain cDNA library to identify proteins interacting with βII-C. We applied stringent selection steps to eliminate false positives and identified 17 proteins that interacted with βII-C (IPβII-C s). The proteins include a fragment (residues 38-284) of “THAP domain containing, apoptosis associated protein 3, isoform CRA g”, “glioma tumor suppressor candidate region gene 2” (residues 1-478), a fragment (residues 74-442) of septin 8 isoform c, a fragment (residues 704-953) of “coatomer protein complex, subunit beta 1, a fragment (residues 146-614) of zinc-finger protein 251, and a fragment (residues 284-435) of syntaxin binding protein 1. We used yeast three-hybrid system to determine the effects of these βII-C interacting proteins as well as of 7 proteins previously identified to interact with the tetramerization region of non-erythroid alpha spectrin (IPαII-N s) [1] on spectrin tetramer formation. The results showed that 3 IPβII-C s were able to bind βII-C even in the presence of αII-N, and 4 IPαII-N s were able to bind αII-N in the presence of βII-C. We also found that the syntaxin binding protein 1 fragment abolished αII-N and βII-C interaction, suggesting that this protein may inhibit or regulate non-erythroid spectrin tetramer formation.

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“…We focused on such proteins which showed domains predicted via the NCBI Conserved Domain Database (https://www.ncbi.nlm.nih.gov/Structure /cdd/wrpsb.cgi; Marchler-Bauer et al, 2011 typically associated with lipolytic enzymes. We identified a total of 22 proteins, i.e.…”

Section: Phospholipases Of Plasmodial Parasitesmentioning

confidence: 99%

Phospholipases during membrane dynamics in malaria parasites

Flammersfeld

Lang

Flieger

et al. 2018

International Journal of Medical Microbiology

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A B S T R A C TPlasmodium parasites, the causative agents of malaria, display a well-regulated lipid metabolism required to ensure their survival in the human host as well as in the mosquito vector. The fine-tuning of lipid metabolic pathways is particularly important for the parasites during the rapid erythrocytic infection cycles, and thus enzymes involved in lipid metabolic processes represent prime targets for malaria chemotherapeutics. While plasmodial enzymes involved in lipid synthesis and acquisition have been studied in the past, to date not much is known about the roles of phospholipases for proliferation and transmission of the malaria parasite. These phospholipid-hydrolyzing esterases are crucial for membrane dynamics during host cell infection and egress by the parasite as well as for replication and cell signaling, and thus they are considered important virulence factors. In this review, we provide a comprehensive bioinformatic analysis of plasmodial phospholipases identified to date. We further summarize previous findings on the lipid metabolism of Plasmodium, highlight the roles of phospholipases during parasite life-cycle progression, and discuss the plasmodial phospholipases as potential targets for malaria therapy.

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CDD: a Conserved Domain Database for the functional annotation of proteins

Cited by 2,796 publications

References 10 publications

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

Non-erythroid beta spectrin interacting proteins and their effects on spectrin tetramerization

Phospholipases during membrane dynamics in malaria parasites

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