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An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37
Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein–protein interaction sites, and it is therefore challenging to understand how M proteins achieve speci...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212996/ https://www.ncbi.nlm.nih.gov/pubmed/35726694 http://dx.doi.org/10.7554/eLife.77989 |
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author | Kolesinski, Piotr Wang, Kuei-Chen Hirose, Yujiro Nizet, Victor Ghosh, Partho |
author_facet | Kolesinski, Piotr Wang, Kuei-Chen Hirose, Yujiro Nizet, Victor Ghosh, Partho |
author_sort | Kolesinski, Piotr |
collection | PubMed |
description | Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein–protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, leading to its neutralization. The crystal structure of a complex of LL-37 with M87 protein, an antigenic M protein variant from a strain that is an emerging threat, revealed a novel interaction mode. The M87 coiled coil unfurled and asymmetrically exposed its hydrophobic core to capture LL-37. A single LL-37 molecule was bound by M87 in the crystal, but in solution additional LL-37 molecules were recruited, consistent with a ‘protein trap’ neutralization mechanism. The interaction mode visualized crystallographically was verified to contribute significantly to LL-37 resistance in an M87 Strep A strain and was identified to be conserved in a number of other M protein types that are prevalent in human populations. Our results provide specific detail for therapeutic inhibition of LL-37 neutralization by M proteins. |
format | Online Article Text |
id | pubmed-9212996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92129962022-06-22 An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 Kolesinski, Piotr Wang, Kuei-Chen Hirose, Yujiro Nizet, Victor Ghosh, Partho eLife Microbiology and Infectious Disease Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein–protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, leading to its neutralization. The crystal structure of a complex of LL-37 with M87 protein, an antigenic M protein variant from a strain that is an emerging threat, revealed a novel interaction mode. The M87 coiled coil unfurled and asymmetrically exposed its hydrophobic core to capture LL-37. A single LL-37 molecule was bound by M87 in the crystal, but in solution additional LL-37 molecules were recruited, consistent with a ‘protein trap’ neutralization mechanism. The interaction mode visualized crystallographically was verified to contribute significantly to LL-37 resistance in an M87 Strep A strain and was identified to be conserved in a number of other M protein types that are prevalent in human populations. Our results provide specific detail for therapeutic inhibition of LL-37 neutralization by M proteins. eLife Sciences Publications, Ltd 2022-06-21 /pmc/articles/PMC9212996/ /pubmed/35726694 http://dx.doi.org/10.7554/eLife.77989 Text en © 2022, Kolesinski et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Microbiology and Infectious Disease Kolesinski, Piotr Wang, Kuei-Chen Hirose, Yujiro Nizet, Victor Ghosh, Partho An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title | An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title_full | An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title_fullStr | An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title_full_unstemmed | An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title_short | An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37 |
title_sort | m protein coiled coil unfurls and exposes its hydrophobic core to capture ll-37 |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212996/ https://www.ncbi.nlm.nih.gov/pubmed/35726694 http://dx.doi.org/10.7554/eLife.77989 |
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