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Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES
Mycobacterium tuberculosis encodes five type VII secretion systems that are responsible for exporting a number of proteins, including members of the Esx family, which have been linked to tuberculosis pathogenesis and survival within host cells. The gene cluster encoding ESX-3 is regulated by the ava...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191040/ https://www.ncbi.nlm.nih.gov/pubmed/21730061 http://dx.doi.org/10.1074/jbc.M111.248732 |
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author | Ilghari, Dariush Lightbody, Kirsty L. Veverka, Vaclav Waters, Lorna C. Muskett, Frederick W. Renshaw, Philip S. Carr, Mark D. |
author_facet | Ilghari, Dariush Lightbody, Kirsty L. Veverka, Vaclav Waters, Lorna C. Muskett, Frederick W. Renshaw, Philip S. Carr, Mark D. |
author_sort | Ilghari, Dariush |
collection | PubMed |
description | Mycobacterium tuberculosis encodes five type VII secretion systems that are responsible for exporting a number of proteins, including members of the Esx family, which have been linked to tuberculosis pathogenesis and survival within host cells. The gene cluster encoding ESX-3 is regulated by the availability of iron and zinc, and secreted protein products such as the EsxG·EsxH complex have been associated with metal ion acquisition. EsxG and EsxH have previously been shown to form a stable 1:1 heterodimeric complex, and here we report the solution structure of the complex, which features a core four-helix bundle decorated at both ends by long, highly flexible, N- and C-terminal arms that contain a number of highly conserved residues. Despite clear similarities in the overall backbone fold to the EsxA·EsxB complex, the structure reveals some striking differences in surface features, including a potential protein interaction site on the surface of the EsxG·EsxH complex. EsxG·EsxH was also found to contain a specific Zn(2+) binding site formed from a cluster of histidine residues on EsxH, which are conserved across obligate mycobacterial pathogens including M. tuberculosis and Mycobacterium leprae. This site may reflect an essential role in zinc ion acquisition or point to Zn(2+)-dependent regulation of its interaction with functional partner proteins. Overall, the surface features of both the EsxG·EsxH and the EsxA·EsxB complexes suggest functions mediated via interactions with one or more target protein partners. |
format | Online Article Text |
id | pubmed-3191040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-31910402011-10-19 Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES Ilghari, Dariush Lightbody, Kirsty L. Veverka, Vaclav Waters, Lorna C. Muskett, Frederick W. Renshaw, Philip S. Carr, Mark D. J Biol Chem Protein Structure and Folding Mycobacterium tuberculosis encodes five type VII secretion systems that are responsible for exporting a number of proteins, including members of the Esx family, which have been linked to tuberculosis pathogenesis and survival within host cells. The gene cluster encoding ESX-3 is regulated by the availability of iron and zinc, and secreted protein products such as the EsxG·EsxH complex have been associated with metal ion acquisition. EsxG and EsxH have previously been shown to form a stable 1:1 heterodimeric complex, and here we report the solution structure of the complex, which features a core four-helix bundle decorated at both ends by long, highly flexible, N- and C-terminal arms that contain a number of highly conserved residues. Despite clear similarities in the overall backbone fold to the EsxA·EsxB complex, the structure reveals some striking differences in surface features, including a potential protein interaction site on the surface of the EsxG·EsxH complex. EsxG·EsxH was also found to contain a specific Zn(2+) binding site formed from a cluster of histidine residues on EsxH, which are conserved across obligate mycobacterial pathogens including M. tuberculosis and Mycobacterium leprae. This site may reflect an essential role in zinc ion acquisition or point to Zn(2+)-dependent regulation of its interaction with functional partner proteins. Overall, the surface features of both the EsxG·EsxH and the EsxA·EsxB complexes suggest functions mediated via interactions with one or more target protein partners. American Society for Biochemistry and Molecular Biology 2011-08-26 2011-07-07 /pmc/articles/PMC3191040/ /pubmed/21730061 http://dx.doi.org/10.1074/jbc.M111.248732 Text en © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Protein Structure and Folding Ilghari, Dariush Lightbody, Kirsty L. Veverka, Vaclav Waters, Lorna C. Muskett, Frederick W. Renshaw, Philip S. Carr, Mark D. Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title | Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title_full | Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title_fullStr | Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title_full_unstemmed | Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title_short | Solution Structure of the Mycobacterium tuberculosis EsxG·EsxH Complex: FUNCTIONAL IMPLICATIONS AND COMPARISONS WITH OTHER M. TUBERCULOSIS Esx FAMILY COMPLEXES |
title_sort | solution structure of the mycobacterium tuberculosis esxg·esxh complex: functional implications and comparisons with other m. tuberculosis esx family complexes |
topic | Protein Structure and Folding |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191040/ https://www.ncbi.nlm.nih.gov/pubmed/21730061 http://dx.doi.org/10.1074/jbc.M111.248732 |
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