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

Luis Franco-Serrano, Juan Cedano, Josep Antoni Perez-Pons, Angel Mozo-Villarias, Jaume Piñol, Isaac Amela, Enrique Querol

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22 Citations (Scopus)


© FEMS 2018. 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.
Original languageEnglish
Article numberfty046
JournalPathogens and Disease
Issue number5
Publication statusPublished - 1 Jul 2018


  • Conservation
  • Epitope
  • Host immune response
  • Moonlighting proteins
  • Vaccines
  • Virulence proteins


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