5df1c94be1a4e4185f92feaee0d31ebe pmc_34203698.pdf 790524e0c2fc7bb0edbbcc60a5a2f29bac11734e pmc_34203698.pdf f01ecddd7c32d983a964388ff7099d9157f561541bca2414c31824f695558f9f pmc_34203698.pdf Title: Pathogen Moonlighting Proteins: From Ancestral Key Metabolic Enzymes to Virulence Factors Subject: Moonlighting and multitasking proteins refer to proteins with two or more functions performed by a single polypeptide chain. An amazing example of the Gain of Function (GoF) phenomenon of these proteins is that 25% of the moonlighting functions of our Multitasking Proteins Database (MultitaskProtDB-II) are related to pathogen virulence activity. Moreover, they usually have a canonical function belonging to highly conserved ancestral key functions, and their moonlighting functions are often involved in inducing extracellular matrix (ECM) protein remodeling. There are three main questions in the context of moonlighting proteins in pathogen virulence: (A) Why are a high percentage of pathogen moonlighting proteins involved in virulence? (B) Why do most of the canonical functions of these moonlighting proteins belong to primary metabolism? Moreover, why are they common in many pathogen species? (C) How are these different protein sequences and structures able to bind the same set of host ECM protein targets, mainly plasminogen (PLG), and colonize host tissues? By means of an extensive bioinformatics analysis, we suggest answers and approaches to these questions. There are three main ideas derived from the work: first, moonlighting proteins are not good candidates for vaccines. Second, several motifs that might be important in the adhesion to the ECM were identified. Third, an overrepresentation of GO codes related with virulence in moonlighting proteins were seen. Keywords: moonlighting proteins; multitasking proteins; microbial pathogens; pathogen virulence factors; vaccines Author: Luis Franco-Serrano, David Sánchez-Redondo, Araceli Nájar-García, Sergio Hernández, Isaac Amela, Josep Antoni Perez-Pons, Jaume Piñol, Angel Mozo-Villarias, Juan Cedano and Enrique Querol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jun 15 10:43:01 2021 CEST ModDate: Tue Jun 15 10:59:16 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1996209 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RKFWJL+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 ODPCOD+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 IVLVDN+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes no 23 0 VCVFNL+VnURWPalladioL Type 1 Custom yes yes no 28 0 SIXRFS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 BGIEFG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 91 0 BGIEGH+PalatinoLinotype TrueType WinAnsi yes yes no 94 0 BGIEGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 97 0 BGIEFG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 118 0 BGIEGH+PalatinoLinotype TrueType WinAnsi yes yes no 121 0 BGIEGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 124 0 BGIEFG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 136 0 BGIEGH+PalatinoLinotype TrueType WinAnsi yes yes no 139 0 BGIEGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 142 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 149 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 159 0 SOSCBV+CMSY10 Type 1 Builtin yes yes no 163 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-09-11 03:06:10 CEST RepresentationInformation: pmc_34203698.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-07-05 03:36:56 CEST Size: 1996209 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 387 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Moonlighting Proteins and Virulence: Questions 1 and 2 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Putative Involvement of Moonlighting Proteins in the Interaction with ECM Proteins, Tissue Colonization, and Metastasis: Question 3 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Tissue Remodeling Strongly Suggests a Parallelism between Microbial Tissue Colonization and Cancer Metastasis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Info: Title: Pathogen Moonlighting Proteins: From Ancestral Key Metabolic Enzymes to Virulence Factors Author: Luis Franco-Serrano, David Sánchez-Redondo, Araceli Nájar-García, Sergio Hernández, Isaac Amela, Josep Antoni Perez-Pons, Jaume Piñol, Angel Mozo-Villarias, Juan Cedano and Enrique Querol Subject: Moonlighting and multitasking proteins refer to proteins with two or more functions performed by a single polypeptide chain. An amazing example of the Gain of Function (GoF) phenomenon of these proteins is that 25% of the moonlighting functions of our Multitasking Proteins Database (MultitaskProtDB-II) are related to pathogen virulence activity. Moreover, they usually have a canonical function belonging to highly conserved ancestral key functions, and their moonlighting functions are often involved in inducing extracellular matrix (ECM) protein remodeling. There are three main questions in the context of moonlighting proteins in pathogen virulence: (A) Why are a high percentage of pathogen moonlighting proteins involved in virulence? (B) Why do most of the canonical functions of these moonlighting proteins belong to primary metabolism? Moreover, why are they common in many pathogen species? (C) How are these different protein sequences and structures able to bind the same set of host ECM protein targets, mainly plasminogen (PLG), and colonize host tissues? By means of an extensive bioinformatics analysis, we suggest answers and approaches to these questions. There are three main ideas derived from the work: first, moonlighting proteins are not good candidates for vaccines. Second, several motifs that might be important in the adhesion to the ECM were identified. Third, an overrepresentation of GO codes related with virulence in moonlighting proteins were seen. 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