Pathogen mimicry of host protein-protein interfaces modulates immunity.
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.
Cancer and Inflammation Program, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: emine.guven-maiorov@nih.gov.
Emine
E
Guven-Maiorov
Cancer and Inflammation Program, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: tsaic@mail.nih.gov.
Chung-Jung
CJ
Tsai
Cancer and Inflammation Program, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Sackler Inst. of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: nussinor@helix.nih.gov.
Ruth
R
Nussinov
D000818:Animals; D005075:Biological Evolution; D054884:Host-Pathogen Interactions; D006801:Humans; D007109:Immunity; D008958:Models, Molecular; D018716:Molecular Mimicry; D011506:Proteins / Q000276:immunology* / Q000378:metabolism*
D011506:Proteins
Host-pathogen interactions; Interface mimicry; Molecular mimicry; Multi-organism; Protein–protein interactions; Structure