ImitateDB: A database for domain and motif mimicry incorporating host and pathogen protein interactions

Tayal, Sonali; Bhatia, Venugopal; Mehrotra, Tanya; Bhatnagar, Sonika

doi:10.1007/s00726-022-03163-3

Cited by 12 publications

(5 citation statements)

References 92 publications

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“…There are also a handful of databases that include information on host – pathogen interactions: HPIDB ( 50 ), PHIDIAS ( 51 ) and PHI-base ( 52 ) contain information about PPIs between the host and pathogen, while ImitateDB ( 53 ) specifically focuses on motif mimicry. These resources contain no or very little data about Leishmania .…”

Section: Discussionmentioning

confidence: 99%

LeishMANIAdb: a comparative resource for Leishmania proteins

Tusnády,

Zeke,

Kálmán

et al. 2023

Database

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Leishmaniasis is a detrimental disease causing serious changes in quality of life and some forms can lead to death. The disease is spread by the parasite Leishmania transmitted by sandfly vectors and their primary hosts are vertebrates including humans. The pathogen penetrates host cells and secretes proteins (the secretome) to repurpose cells for pathogen growth and to alter cell signaling via host–pathogen protein–protein interactions). Here, we present LeishMANIAdb, a database specifically designed to investigate how Leishmania virulence factors may interfere with host proteins. Since the secretomes of different Leishmania species are only partially characterized, we collated various experimental evidence and used computational predictions to identify Leishmania secreted proteins to generate a user-friendly unified web resource allowing users to access all information available on experimental and predicted secretomes. In addition, we manually annotated host–pathogen interactions of 211 proteins and the localization/function of 3764 transmembrane (TM) proteins of different Leishmania species. We also enriched all proteins with automatic structural and functional predictions that can provide new insights in the molecular mechanisms of infection. Our database may provide novel insights into Leishmania host–pathogen interactions and help to identify new therapeutic targets for this neglected disease. Database URL https://leishmaniadb.ttk.hu/

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Section: Discussionmentioning

confidence: 99%

LeishMANIAdb: a comparative resource for Leishmania proteins

Tusnády,

Zeke,

Kálmán

et al. 2023

Database

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“…Although the ELM acronym means "eukaryotic linear motif", the search for ELMs is also useful for studies on pathogenic prokaryotes, since pathogens mimic features of critical host proteins to hijack their cell machinery, promoting infection of the host [66,[117][118][119]. Effectors that do not share high overall sequence identity, but share motifs, domains or similar tridimensional structures, may share similar functions and are termed "functional orthologs" [120].…”

Section: Discussionmentioning

confidence: 99%

Novel Insights into Phytoplasma Effectors

Carreón-Anguiano,

Vila-Luna,

Sáenz-Carbonell

et al. 2023

Horticulturae

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Effectoromics has become integral to the identification of pathogen targets and/or host-resistant proteins for the genetic improvement of plants in agriculture and horticulture. Phytoplasmas are the causal agents of more than 100 plant diseases in economically important crops such as vegetables, spices, medicinal plants, ornamentals, palms, fruit trees, etc. To date, around 20 effectors in phytoplasmas have been experimentally validated but the list of putative effectors comprises hundreds of different proteins. Very few families (tribes) have been identified based on homology, such as the SAP05-like, SAP11-like, SAP54-like and TENGU-like families. The lack of conservation in amino acid sequences slows the progress of effectoromics in phytoplasmas since many effectors must be studied individually. Here, 717 phytoplasma effector candidates and 21 validated effectors were characterized in silico to identify common features. We identified functional domains in 153 effectors, while 585 had no known domains. The most frequently identified domain was the sequence-variable mosaic domain (SVM domain), widely distributed in 87 phytoplasma effectors. Searching for de novo amino acid motifs, 50 were found in the phytoplasma effector dataset; 696 amino acid sequences of effectors had at least 1 motif while 42 had no motif at all. These data allowed us to organize effectors into 15 tribes, uncovering, for the first time, evolutionary relationships largely masked by lack of sequence conservation among effectors. We also identified 42 eukaryotic linear motifs (ELMs) in phytoplasma effector sequences. Since the motifs are related to common functions, this novel organization of phytoplasma effectors may help further advance effectoromics research to combat phytoplasma infection in agriculture and horticulture.

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“…One of the earliest reports of molecular mimicry came from the parasitic nematode Ascaris lumbricoides , which possesses A- and B-like blood group antigens in its polysaccharides (Oliver-González, 1944). The definition of molecular mimicry has adapted to keep up with molecular and genomic technologies and is now widely considered to similarity between proteins at the level of primary structure (amino acid sequence) and tertiary structure (summarized in (Tayal et al, 2022)). An assumption is that molecular mimicry confers a fitness benefit to the pathogen.…”

Section: Introductionmentioning

confidence: 99%

Proteome-wide comparison of tertiary protein structures reveal extensive molecular mimicry inPlasmodium-human interactions

Muthye

Wasmuth

2023

Preprint

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Molecular mimicry is a strategy used by parasites to escape the host immune system and successfully transmit to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, with advances in the prediction of tertiary structural models, led by Deepmind's AlphaFold, it is now possible to compare the tertiary structures of thousands of proteins from parasites and their hosts, to identify more subtle mimics. Here, we present the first proteome-level search for tertiary structure similarity between the proteins from Plasmodium falciparum and human. Of 206 P. falciparum proteins that have previously been proposed as mediators of Plasmodium-human interactions, we propose that seven evolved to molecularly mimic a human protein. By expanding the approach to all P. falciparum proteins, we identified a further 386 potential mimics, with 51 proteins corroborated by additional biological data. These findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.

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ImitateDB: A database for domain and motif mimicry incorporating host and pathogen protein interactions

Cited by 12 publications

References 92 publications

LeishMANIAdb: a comparative resource for Leishmania proteins

LeishMANIAdb: a comparative resource for Leishmania proteins

Novel Insights into Phytoplasma Effectors

Proteome-wide comparison of tertiary protein structures reveal extensive molecular mimicry inPlasmodium-human interactions

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