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Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins

The initiation of infection of host tissues by Staphylococcus aureus requires a family of staphylococcal adhesive proteins containing serine–aspartate repeat (SDR) domains, such as ClfA. The O-linked glycosylation of the long-chain SDR domain mediated by SdgB and SdgA is a key virulence factor that...

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Autores principales: Kim, Dong-Gyun, Baek, Inwha, Lee, Yeon, Kim, Hyerry, Kim, Jin Young, Bang, Geul, Kim, Sunghwan, Yoon, Hye Jin, Han, Byung Woo, Suh, Se Won, Kim, Hyoun Sook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561734/
https://www.ncbi.nlm.nih.gov/pubmed/34726173
http://dx.doi.org/10.1107/S2059798321010068
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author Kim, Dong-Gyun
Baek, Inwha
Lee, Yeon
Kim, Hyerry
Kim, Jin Young
Bang, Geul
Kim, Sunghwan
Yoon, Hye Jin
Han, Byung Woo
Suh, Se Won
Kim, Hyoun Sook
author_facet Kim, Dong-Gyun
Baek, Inwha
Lee, Yeon
Kim, Hyerry
Kim, Jin Young
Bang, Geul
Kim, Sunghwan
Yoon, Hye Jin
Han, Byung Woo
Suh, Se Won
Kim, Hyoun Sook
author_sort Kim, Dong-Gyun
collection PubMed
description The initiation of infection of host tissues by Staphylococcus aureus requires a family of staphylococcal adhesive proteins containing serine–aspartate repeat (SDR) domains, such as ClfA. The O-linked glycosylation of the long-chain SDR domain mediated by SdgB and SdgA is a key virulence factor that protects the adhesive SDR proteins against host proteolytic attack in order to promote successful tissue colonization, and has also been implicated in staphylococcal agglutination, which leads to sepsis and an immunodominant epitope for a strong antibody response. Despite the biological significance of these two glycosyltransferases involved in pathogenicity and avoidance of the host innate immune response, their structures and the molecular basis of their activity have not been investigated. This study reports the crystal structures of SdgB and SdgA from S. aureus as well as multiple structures of SdgB in complex with its substrates (for example UDP, N-acetylglucosamine or SDR peptides), products (glycosylated SDR peptides) or phosphate ions. Together with biophysical and biochemical analyses, this structural work uncovered the novel mechanism by which SdgB and SdgA carry out the glycosyl-transfer process to the long SDR region in SDR proteins. SdgB undergoes dynamic changes in its structure such as a transition from an open to a closed conformation upon ligand binding and takes diverse forms, both as a homodimer and as a heterodimer with SdgA. Overall, these findings not only elucidate the putative role of the three domains of SdgB in recognizing donor and acceptor substrates, but also provide new mechanistic insights into glycosylation of the SDR domain, which can serve as a starting point for the development of antibacterial drugs against staphylococcal infections.
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spelling pubmed-85617342021-11-18 Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins Kim, Dong-Gyun Baek, Inwha Lee, Yeon Kim, Hyerry Kim, Jin Young Bang, Geul Kim, Sunghwan Yoon, Hye Jin Han, Byung Woo Suh, Se Won Kim, Hyoun Sook Acta Crystallogr D Struct Biol Research Papers The initiation of infection of host tissues by Staphylococcus aureus requires a family of staphylococcal adhesive proteins containing serine–aspartate repeat (SDR) domains, such as ClfA. The O-linked glycosylation of the long-chain SDR domain mediated by SdgB and SdgA is a key virulence factor that protects the adhesive SDR proteins against host proteolytic attack in order to promote successful tissue colonization, and has also been implicated in staphylococcal agglutination, which leads to sepsis and an immunodominant epitope for a strong antibody response. Despite the biological significance of these two glycosyltransferases involved in pathogenicity and avoidance of the host innate immune response, their structures and the molecular basis of their activity have not been investigated. This study reports the crystal structures of SdgB and SdgA from S. aureus as well as multiple structures of SdgB in complex with its substrates (for example UDP, N-acetylglucosamine or SDR peptides), products (glycosylated SDR peptides) or phosphate ions. Together with biophysical and biochemical analyses, this structural work uncovered the novel mechanism by which SdgB and SdgA carry out the glycosyl-transfer process to the long SDR region in SDR proteins. SdgB undergoes dynamic changes in its structure such as a transition from an open to a closed conformation upon ligand binding and takes diverse forms, both as a homodimer and as a heterodimer with SdgA. Overall, these findings not only elucidate the putative role of the three domains of SdgB in recognizing donor and acceptor substrates, but also provide new mechanistic insights into glycosylation of the SDR domain, which can serve as a starting point for the development of antibacterial drugs against staphylococcal infections. International Union of Crystallography 2021-10-20 /pmc/articles/PMC8561734/ /pubmed/34726173 http://dx.doi.org/10.1107/S2059798321010068 Text en © Dong-Gyun Kim et al. 2021 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
spellingShingle Research Papers
Kim, Dong-Gyun
Baek, Inwha
Lee, Yeon
Kim, Hyerry
Kim, Jin Young
Bang, Geul
Kim, Sunghwan
Yoon, Hye Jin
Han, Byung Woo
Suh, Se Won
Kim, Hyoun Sook
Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title_full Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title_fullStr Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title_full_unstemmed Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title_short Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins
title_sort structural basis for sdgb- and sdga-mediated glycosylation of staphylococcal adhesive proteins
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561734/
https://www.ncbi.nlm.nih.gov/pubmed/34726173
http://dx.doi.org/10.1107/S2059798321010068
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