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A hypothesis explaining why so many pathogen virulence proteins are moonlighting proteins
Franco-Serrano, Luís (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cedano Rodríguez, Juan Antonio (Universidad de la República Regional Norte-Salto. Laboratorio de Inmunología)
Pérez-Pons, Josep A. (Josep Antoni) (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mozo Villarias, Ángel (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Piñol Ribas, Jaume (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Amela, Isaac (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Querol Murillo, Enric (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Fecha: 2018
Resumen: 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.
Nota: Número d'acord de subvenció MINECO/BIO2017-84166-R
Nota: Número d'acord de subvenció MINECO/BFU2013-50176-EXP
Nota: Número d'acord de subvenció MINECO/BIO2013-48704-R
Derechos: This is an article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Materia: Moonlighting proteins ; Vaccines ; Virulence proteins ; Host immune response ; Epitope ; Conservation
Publicado en: Pathogens and disease, Vol. 76, issue 5 (July 2018) , ISSN 2049-632X

PMID: 29718264
DOI: 10.1093/femspd/fty046


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