Pathogen mimicry of host protein-protein interfaces modulates immunity

Emine Guven-Maiorov, Chung Jung Tsai, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Signaling pathways shape and transmit the cell's reaction to its changing environment; however, pathogens can circumvent this response by manipulating host signaling. To subvert host defense, they beat it at its own game: they hijack host pathways by mimicking the binding surfaces of host-encoded proteins. For this, it is not necessary to achieve global protein homology; imitating merely the interaction surface is sufficient. Different protein folds often interact via similar protein–protein interface architectures. This similarity in binding surfaces permits the pathogenic protein to compete with a host target protein. Thus, rather than binding a host-encoded partner, the host protein hub binds the pathogenic surrogate. The outcome can be dire: rewiring or repurposing the host pathways, shifting the cell signaling landscape and consequently the immune response. They can also cause persistent infections as well as cancer by modulating key signaling pathways, such as those involving Ras. Mapping the rewired host-pathogen ‘superorganism’ interaction network – along with its structural details – is critical for in-depth understanding of pathogenic mechanisms and developing efficient therapeutics. Here, we overview the role of molecular mimicry in pathogen host evasion as well as types of molecular mimicry mechanisms that emerged during evolution.

Original languageEnglish
Pages (from-to)136-145
Number of pages10
JournalSeminars in Cell and Developmental Biology
Volume58
DOIs
StatePublished - 1 Oct 2016

Funding

FundersFunder number
Center for Cancer Research
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010441

    Keywords

    • Host-pathogen interactions
    • Interface mimicry
    • Molecular mimicry
    • Multi-organism
    • Protein–protein interactions
    • Structure

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