Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation
Background: The mycobacterial PE_PGRS protein family is present only in pathogenic strains of the genus mycobacterium, such as <i>Mtb</i> and members of the MTB complex, suggesting a likely important role of this family in pathogenesis. Their PGRS domains are highly polymorphic and have...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/5/812 |
| _version_ | 1797600850229592064 |
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| author | Eliza Kramarska Flavio De Maio Giovanni Delogu Rita Berisio |
| author_facet | Eliza Kramarska Flavio De Maio Giovanni Delogu Rita Berisio |
| author_sort | Eliza Kramarska |
| collection | DOAJ |
| description | Background: The mycobacterial PE_PGRS protein family is present only in pathogenic strains of the genus mycobacterium, such as <i>Mtb</i> and members of the MTB complex, suggesting a likely important role of this family in pathogenesis. Their PGRS domains are highly polymorphic and have been suggested to cause antigenic variations and facilitate pathogen survival. The availability of AlphaFold2.0 offered us a unique opportunity to better understand structural and functional properties of these domains and a role of polymorphism in <i>Mtb</i> evolution and dissemination. Methods: We made extensive use of AlphaFold2.0 computations and coupled them with sequence distribution phylogenetic and frequency analyses, and antigenic predictions. Results: Modeling of several polymorphic forms of PE_PGRS33, the prototype of the PE_PGRS family and sequence analyses allowed us to predict the structural impact of mutations/deletions/insertions present in the most frequent variants. These analyses well correlate with the observed frequency and with the phenotypic features of the described variants. Conclusions: Here, we provide a thorough description of structural impacts of the observed polymorphism of PE_PGRS33 protein and we correlate predicted structures to the known fitness of strains containing specific variants. Finally, we also identify protein variants associated with bacterial evolution, showing sophisticated modifications likely endowed with a gain-of-function role during bacterial evolution. |
| first_indexed | 2024-03-11T03:54:46Z |
| format | Article |
| id | doaj.art-6ca8ec6fa45543289ee530b57e77e159 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T03:54:46Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-6ca8ec6fa45543289ee530b57e77e1592023-11-18T00:39:33ZengMDPI AGBiomolecules2218-273X2023-05-0113581210.3390/biom13050812Structural Basis of PE_PGRS Polymorphism, a Tool for Functional ModulationEliza Kramarska0Flavio De Maio1Giovanni Delogu2Rita Berisio3Institute of Biostructures and Bioimaging, IBB, CNR, 80131 Naples, ItalyDipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, ItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche E Perioperatorie—Sezione di Microbiologia, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyInstitute of Biostructures and Bioimaging, IBB, CNR, 80131 Naples, ItalyBackground: The mycobacterial PE_PGRS protein family is present only in pathogenic strains of the genus mycobacterium, such as <i>Mtb</i> and members of the MTB complex, suggesting a likely important role of this family in pathogenesis. Their PGRS domains are highly polymorphic and have been suggested to cause antigenic variations and facilitate pathogen survival. The availability of AlphaFold2.0 offered us a unique opportunity to better understand structural and functional properties of these domains and a role of polymorphism in <i>Mtb</i> evolution and dissemination. Methods: We made extensive use of AlphaFold2.0 computations and coupled them with sequence distribution phylogenetic and frequency analyses, and antigenic predictions. Results: Modeling of several polymorphic forms of PE_PGRS33, the prototype of the PE_PGRS family and sequence analyses allowed us to predict the structural impact of mutations/deletions/insertions present in the most frequent variants. These analyses well correlate with the observed frequency and with the phenotypic features of the described variants. Conclusions: Here, we provide a thorough description of structural impacts of the observed polymorphism of PE_PGRS33 protein and we correlate predicted structures to the known fitness of strains containing specific variants. Finally, we also identify protein variants associated with bacterial evolution, showing sophisticated modifications likely endowed with a gain-of-function role during bacterial evolution.https://www.mdpi.com/2218-273X/13/5/812protein structuretuberculosispolymorphismPE_PGRS |
| spellingShingle | Eliza Kramarska Flavio De Maio Giovanni Delogu Rita Berisio Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation Biomolecules protein structure tuberculosis polymorphism PE_PGRS |
| title | Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation |
| title_full | Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation |
| title_fullStr | Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation |
| title_full_unstemmed | Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation |
| title_short | Structural Basis of PE_PGRS Polymorphism, a Tool for Functional Modulation |
| title_sort | structural basis of pe pgrs polymorphism a tool for functional modulation |
| topic | protein structure tuberculosis polymorphism PE_PGRS |
| url | https://www.mdpi.com/2218-273X/13/5/812 |
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