Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response
A growing body of evidence supports the hypothesis that intrinsically disordered proteins often mediate host–pathogen interactions and modulate host functions for pathogen survival and virulence. Mycobacterium tuberculosis (M.tb) has evolved largely through reductive evolution, with a few exceptions...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12749 |
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| author | Javeed Ahmad Mohd Khubaib Javaid Ahmad Sheikh Rita Pancsa Saroj Kumar Alagiri Srinivasan Mohan Madan Babu Seyed E. Hasnain Nasreen Z. Ehtesham |
| author_facet | Javeed Ahmad Mohd Khubaib Javaid Ahmad Sheikh Rita Pancsa Saroj Kumar Alagiri Srinivasan Mohan Madan Babu Seyed E. Hasnain Nasreen Z. Ehtesham |
| author_sort | Javeed Ahmad |
| collection | DOAJ |
| description | A growing body of evidence supports the hypothesis that intrinsically disordered proteins often mediate host–pathogen interactions and modulate host functions for pathogen survival and virulence. Mycobacterium tuberculosis (M.tb) has evolved largely through reductive evolution, with a few exceptions such as the glycine–alanine‐rich PE–PPE/PGRS protein family, which has been expanding in pathogenic mycobacteria. Here, our analyses of the M.tb proteome and secretome revealed that the PE–PGRS subfamily is enriched for disordered regions and disordered binding sites, pointing to their importance in host–pathogen interactions. As a case study, the secondary structure of PE35–PPE68 and PE32–PPE65 of the pathogenesis‐related RD1 and RD8 regions was analyzed through Fourier‐transform infrared spectroscopy. These disordered proteins displayed a considerable structural shift from disordered to ordered while engaged in the formation of complexes. While these proteins are immunogenic individually and enhance the pro‐pathogen response, their corresponding complexes enhanced the responses manifold as displayed here by PE35 and PPE68. It is likely that M.tb exploits such disorder–order structural dynamics as a strategy to mount a pro‐pathogen response and subvert host defense for productive infection. This functional gain also serves as a means to compensate genomic content loss due to reductive evolution. |
| first_indexed | 2024-04-10T00:37:11Z |
| format | Article |
| id | doaj.art-2fac3cb98bcb4b81b7511515a5e073a3 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2025-02-17T19:59:51Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-2fac3cb98bcb4b81b7511515a5e073a32024-12-09T14:15:33ZengWileyFEBS Open Bio2211-54632020-01-01101708510.1002/2211-5463.12749Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune responseJaveed Ahmad0Mohd Khubaib1Javaid Ahmad Sheikh2Rita Pancsa3Saroj Kumar4Alagiri Srinivasan5Mohan Madan Babu6Seyed E. Hasnain7Nasreen Z. Ehtesham8Inflammation Biology and Cell Signalling Laboratory National Institute of Pathology New Delhi IndiaJH Institute of Molecular Medicine Jamia Hamdard New Delhi IndiaInflammation Biology and Cell Signalling Laboratory National Institute of Pathology New Delhi IndiaMedical Research Council, Laboratory of Molecular Biology Cambridge UKDepartment of Biophysics All India Institute of Medical Sciences New Delhi IndiaDepartment of Biophysics All India Institute of Medical Sciences New Delhi IndiaMedical Research Council, Laboratory of Molecular Biology Cambridge UKJH Institute of Molecular Medicine Jamia Hamdard New Delhi IndiaInflammation Biology and Cell Signalling Laboratory National Institute of Pathology New Delhi IndiaA growing body of evidence supports the hypothesis that intrinsically disordered proteins often mediate host–pathogen interactions and modulate host functions for pathogen survival and virulence. Mycobacterium tuberculosis (M.tb) has evolved largely through reductive evolution, with a few exceptions such as the glycine–alanine‐rich PE–PPE/PGRS protein family, which has been expanding in pathogenic mycobacteria. Here, our analyses of the M.tb proteome and secretome revealed that the PE–PGRS subfamily is enriched for disordered regions and disordered binding sites, pointing to their importance in host–pathogen interactions. As a case study, the secondary structure of PE35–PPE68 and PE32–PPE65 of the pathogenesis‐related RD1 and RD8 regions was analyzed through Fourier‐transform infrared spectroscopy. These disordered proteins displayed a considerable structural shift from disordered to ordered while engaged in the formation of complexes. While these proteins are immunogenic individually and enhance the pro‐pathogen response, their corresponding complexes enhanced the responses manifold as displayed here by PE35 and PPE68. It is likely that M.tb exploits such disorder–order structural dynamics as a strategy to mount a pro‐pathogen response and subvert host defense for productive infection. This functional gain also serves as a means to compensate genomic content loss due to reductive evolution.https://doi.org/10.1002/2211-5463.12749folding‐upon‐bindingimmune modulationimmunogenicityMycobacterium tuberculosispathogenesisprotein–protein interaction |
| spellingShingle | Javeed Ahmad Mohd Khubaib Javaid Ahmad Sheikh Rita Pancsa Saroj Kumar Alagiri Srinivasan Mohan Madan Babu Seyed E. Hasnain Nasreen Z. Ehtesham Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response FEBS Open Bio folding‐upon‐binding immune modulation immunogenicity Mycobacterium tuberculosis pathogenesis protein–protein interaction |
| title | Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response |
| title_full | Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response |
| title_fullStr | Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response |
| title_full_unstemmed | Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response |
| title_short | Disorder‐to‐order transition in PE–PPE proteins of Mycobacterium tuberculosis augments the pro‐pathogen immune response |
| title_sort | disorder to order transition in pe ppe proteins of mycobacterium tuberculosis augments the pro pathogen immune response |
| topic | folding‐upon‐binding immune modulation immunogenicity Mycobacterium tuberculosis pathogenesis protein–protein interaction |
| url | https://doi.org/10.1002/2211-5463.12749 |
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