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

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Abstract

Molecular mimicry of host proteins by pathogens constitutes a strategy to hijack the host pathways. At present, there is no dedicated resource for mimicked domains and motifs in the host–pathogen interactome. In this work, the experimental host–pathogen (HP) and host–host (HH) protein–protein interactions (PPIs) were collated. The domains and motifs of these proteins were annotated using CD Search and ScanProsite, respectively. Host and pathogen proteins with a shared host interactor and similar domain/motif constitute a mimicry pair exhibiting global structural similarity (domain mimicry pair; DMP) or local sequence motif similarity (motif mimicry pair; MMP). Mimicry pairs are likely to be co-expressed and co-localized. 1,97,607 DMPs and 32,67,568 MMPs were identified in 49,265 experimental HP-PPIs and organized in a web-based resource, ImitateDB (http://imitatedb.sblab-nsit.net) that can be easily queried. The results are externally integrated using hyperlinked domain PSSM ID, motif ID, protein ID and PubMed ID. Kinase, UL36, Smc and DEXDc were frequent DMP domains whereas protein kinase C phosphorylation, casein kinase 2 phosphorylation, glycosylation and myristoylation sites were frequent MMP motifs. Novel DMP domains SANT, Tudor, PhoX and MMP motif microbody C-terminal targeting signal, cornichon signature and lipocalin signature were proposed. ImitateDB is a novel resource for identifying mimicry in interacting host and pathogen proteins.

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Data availability

The authors confirm that the data supporting the findings of this study are available at http://imitatedb.sblab-nsit.net. The python script for the identification of DMP/MMP is available at the following link: https://github.com/sblab/ImitateDB.git. At present, Imitate DB contains information from HP-PPIs up to April 2021. We plan to update this database regularly as new releases of the contributing databases become available. Apart from collating all the HP-PPIs from different databases, we are working towards mining the HP-PPIs from literature for computation of additional DMPs and MMPs. We plan to compute DMPs and MMPs for predicted HP-PPIs. Work is also ongoing for providing information on DMPs/MMPs for Sars-CoV-2.

Abbreviations

HP-PPI:

Host–pathogen protein–protein interaction

HHI:

Host–host interaction

DMP:

Domain mimicry pair

MMP:

Motif mimicry pair

SANT:

Swi3, Ada2, N-Cor, and TFIIIB

CD search:

Conserved domain search

PSSM:

Position-specific scoring matrices

COG:

Cluster of orthologs

PKC:

Protein kinase C

CK2:

Casein kinase II

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Acknowledgements

ST acknowledges Netaji Subhas University of Technology for grant of Teaching cum Research Fellowship. SB acknowledges Indian Council of Medical Research for project Grant ID 2021-6412.

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  1. Sonali Tayal and Venugopal Bhatia share equal first authorship.

Authors and Affiliations

  1. Computational and Structural Biology Laboratory, Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, Dwarka, New Delhi, 110078, India

    Sonali Tayal, Tanya Mehrotra & Sonika Bhatnagar

  2. Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, 110078, India

    Venugopal Bhatia & Sonika Bhatnagar

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  1. Sonali Tayal
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  2. Venugopal Bhatia
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Contributions

ST: carried out data cleaning, enrichment and organisation, development of the database, analysis, and manuscript preparation. VB: developed the backend and front end of the web interface. TM: carried out data acquisition and cleaning. SB: was involved in conception, design, analysis, and supervision of the study. The manuscript was reviewed by all the authors.

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Correspondence to Sonika Bhatnagar.

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Tayal, S., Bhatia, V., Mehrotra, T. et al. ImitateDB: A database for domain and motif mimicry incorporating host and pathogen protein interactions. Amino Acids 54, 923–934 (2022). https://doi.org/10.1007/s00726-022-03163-3

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