Large-scale survey for potentially targetable indels in bacterial and protozoan proteins

Authors

  • Artem Cherkasov,

    Corresponding author
    1. Department of Medicine (Division of Infectious Diseases), University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
    • Division of Infectious Diseases, University of British Columbia, 2733 Heather Street, Vancouver, BC, Canada V5Z 3J5
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  • Shang-Jung Lee,

    1. Department of Medicine (Division of Infectious Diseases), University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
    2. Strategic Training Program in Bioinformatics, University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
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  • Devki Nandan,

    1. Department of Medicine (Division of Infectious Diseases), University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
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  • Neil E. Reiner

    1. Department of Medicine (Division of Infectious Diseases), University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
    2. Microbiology and Immunology, University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada
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Abstract

Our previous results demonstrated that some essential, housekeeping proteins from pathogenic microorganisms may contain sizable insertions–deletions in their sequences (compared to close human homologs) that can be responsible for unexpected virulence properties. For example, we found that indel-bearing elongation factor-1α from several pathogenic protozoa can activate a human tyrosine phosphatase SHP-1 leading to deactivation of macrophages. On the one hand, these findings allowed development of a strategy for targeting some indel-containing pathogen proteins that have similar human counterparts. On the other hand, the results raised numerous questions regarding the nature and implications of sequence indels in pathogen proteins. In the present study, we conducted a large-scale survey of indels in proteins from 136 bacterial and protozoan genomes. It has been established that sizable insertions and deletions occur in approximately 5–10% of bacterial proteins with close human homologs, while proteins from the protozoan pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania donovani exhibit elevated indel content that can reach up to 25%. The finding suggested that the occurrence of sequence indels may be involved in the evolution of pathogenic mechanisms in these protozoa. Proteins 2006. © 2005 Wiley-Liss, Inc.

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