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Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains

Recent advancements in vaccinology have led to the development of the M72/AS01E subunit vaccine, of which the major component is the Mycobacterium tuberculosis (MTB) PPE18 protein. Previous studies have demonstrated the genetic variability of the gene encoding PPE18 protein and the resulting peptide...

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Autores principales: Hakim, Jill M. C., Yang, Zhenhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819968/
https://www.ncbi.nlm.nih.gov/pubmed/33488541
http://dx.doi.org/10.3389/fmicb.2020.595312
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author Hakim, Jill M. C.
Yang, Zhenhua
author_facet Hakim, Jill M. C.
Yang, Zhenhua
author_sort Hakim, Jill M. C.
collection PubMed
description Recent advancements in vaccinology have led to the development of the M72/AS01E subunit vaccine, of which the major component is the Mycobacterium tuberculosis (MTB) PPE18 protein. Previous studies have demonstrated the genetic variability of the gene encoding PPE18 protein and the resulting peptide changes in diverse clinical strains of MTB; however, none have modeled the structural changes resulting from these peptide changes and their immunological implications. In this study, we investigated the structural predictions of 29 variant PPE18 proteins previously reported. We found evidence that PPE18 is at least a two-domain protein, with a highly conserved first domain and a largely variable second domain that has different coevolutionary clusters. Further, we investigated putative epitope sites in the clinical variants of PPE18 using prediction software. We found a negative relationship between T-cell epitope number and residue variability, while B-cell epitope likelihood was positively correlated with residue variability. Moreover, we found far more residues in the second domain predicted to be B-cell epitopes compared with the first domain. These results suggest an important functional role of the first domain and a role in immune evasion for the second, which extends our knowledge base of the basic biology of the PPE18 protein and indicates the need for further study into non-traditional immunological responses to TB.
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spelling pubmed-78199682021-01-23 Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains Hakim, Jill M. C. Yang, Zhenhua Front Microbiol Microbiology Recent advancements in vaccinology have led to the development of the M72/AS01E subunit vaccine, of which the major component is the Mycobacterium tuberculosis (MTB) PPE18 protein. Previous studies have demonstrated the genetic variability of the gene encoding PPE18 protein and the resulting peptide changes in diverse clinical strains of MTB; however, none have modeled the structural changes resulting from these peptide changes and their immunological implications. In this study, we investigated the structural predictions of 29 variant PPE18 proteins previously reported. We found evidence that PPE18 is at least a two-domain protein, with a highly conserved first domain and a largely variable second domain that has different coevolutionary clusters. Further, we investigated putative epitope sites in the clinical variants of PPE18 using prediction software. We found a negative relationship between T-cell epitope number and residue variability, while B-cell epitope likelihood was positively correlated with residue variability. Moreover, we found far more residues in the second domain predicted to be B-cell epitopes compared with the first domain. These results suggest an important functional role of the first domain and a role in immune evasion for the second, which extends our knowledge base of the basic biology of the PPE18 protein and indicates the need for further study into non-traditional immunological responses to TB. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7819968/ /pubmed/33488541 http://dx.doi.org/10.3389/fmicb.2020.595312 Text en Copyright © 2021 Hakim and Yang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hakim, Jill M. C.
Yang, Zhenhua
Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title_full Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title_fullStr Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title_full_unstemmed Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title_short Predicted Structural Variability of Mycobacterium tuberculosis PPE18 Protein With Immunological Implications Among Clinical Strains
title_sort predicted structural variability of mycobacterium tuberculosis ppe18 protein with immunological implications among clinical strains
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819968/
https://www.ncbi.nlm.nih.gov/pubmed/33488541
http://dx.doi.org/10.3389/fmicb.2020.595312
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