A hypothesis explaining why so many pathogen virulence proteins are moonlighting proteins

Abstract Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit moonlighting phenomenon. We have collected 69...

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Bibliographic Details
Published in:Pathogens and disease 2018-07, Vol.76 (5)
Main Authors: Franco-Serrano, Luis, Cedano, Juan, Perez-Pons, Josep Antoni, Mozo-Villarias, Angel, Piñol, Jaume, Amela, Isaac, Querol, Enrique
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Autoimmune diseases
Databases, Factual
Epitopes
Host-Pathogen Interactions
Hypotheses
Immune Evasion
Immune response
Immune system
Metabolic pathways
Metabolism
Mimicry
Multitasking
Pathogens
Proteins
Vaccines
Virulence
Virulence Factors - immunology
Virulence Factors - metabolism
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Summary:Abstract Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit moonlighting phenomenon. We have collected 698 moonlighting proteins in MultitaskProtDB-II database. A survey shows that 25% of the proteins of the database correspond to moonlighting functions related to pathogens virulence activity. Why is the canonical function of these virulence proteins mainly from ancestral key biological functions (especially of primary metabolism)? Our hypothesis is that these proteins present a high conservation between the pathogen protein and the host counterparts. Therefore, the host immune system will not elicit protective antibodies against pathogen proteins. The fact of sharing epitopes with host proteins (known as epitope mimicry) might be the cause of autoimmune diseases. Although many pathogen proteins can be antigenic, only a few of them would elicit a protective immune response. This would also explain the lack of successful vaccines based in these conserved moonlighting proteins. This review looks at why so many pathogen virulence proteins are from the primary metabolism and are conserved between pathogen and host.
ISSN:2049-632X
2049-632X
DOI:10.1093/femspd/fty046