Cargando…
Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF
The Staphylococcus aureus cell wall-anchored adhesin ClfA binds to the very large blood circulating protein, von Willebrand factor (vWF) via vWF-binding protein (vWbp), a secreted protein that does not bind the cell wall covalently. Here we perform force spectroscopy studies on living bacteria to un...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041789/ https://www.ncbi.nlm.nih.gov/pubmed/33846500 http://dx.doi.org/10.1038/s42003-021-01986-6 |
_version_ | 1783678008546033664 |
---|---|
author | Viljoen, Albertus Viela, Felipe Mathelié-Guinlet, Marion Missiakas, Dominique Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. |
author_facet | Viljoen, Albertus Viela, Felipe Mathelié-Guinlet, Marion Missiakas, Dominique Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. |
author_sort | Viljoen, Albertus |
collection | PubMed |
description | The Staphylococcus aureus cell wall-anchored adhesin ClfA binds to the very large blood circulating protein, von Willebrand factor (vWF) via vWF-binding protein (vWbp), a secreted protein that does not bind the cell wall covalently. Here we perform force spectroscopy studies on living bacteria to unravel the molecular mechanism of this interaction. We discover that the presence of all three binding partners leads to very high binding forces (2000 pN), largely outperforming other known ternary complexes involving adhesins. Strikingly, our experiments indicate that a direct interaction involving features of the dock, lock and latch mechanism must occur between ClfA and vWF to sustain the extreme tensile strength of the ternary complex. Our results support a previously undescribed mechanism whereby vWbp activates a direct, ultra-strong interaction between ClfA and vWF. This intriguing interaction represents a potential target for therapeutic interventions, including synthetic peptides inhibiting the ultra-strong interactions between ClfA and its ligands. |
format | Online Article Text |
id | pubmed-8041789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80417892021-04-28 Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF Viljoen, Albertus Viela, Felipe Mathelié-Guinlet, Marion Missiakas, Dominique Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. Commun Biol Article The Staphylococcus aureus cell wall-anchored adhesin ClfA binds to the very large blood circulating protein, von Willebrand factor (vWF) via vWF-binding protein (vWbp), a secreted protein that does not bind the cell wall covalently. Here we perform force spectroscopy studies on living bacteria to unravel the molecular mechanism of this interaction. We discover that the presence of all three binding partners leads to very high binding forces (2000 pN), largely outperforming other known ternary complexes involving adhesins. Strikingly, our experiments indicate that a direct interaction involving features of the dock, lock and latch mechanism must occur between ClfA and vWF to sustain the extreme tensile strength of the ternary complex. Our results support a previously undescribed mechanism whereby vWbp activates a direct, ultra-strong interaction between ClfA and vWF. This intriguing interaction represents a potential target for therapeutic interventions, including synthetic peptides inhibiting the ultra-strong interactions between ClfA and its ligands. Nature Publishing Group UK 2021-04-12 /pmc/articles/PMC8041789/ /pubmed/33846500 http://dx.doi.org/10.1038/s42003-021-01986-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Viljoen, Albertus Viela, Felipe Mathelié-Guinlet, Marion Missiakas, Dominique Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title | Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title_full | Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title_fullStr | Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title_full_unstemmed | Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title_short | Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF |
title_sort | staphylococcus aureus vwf-binding protein triggers a strong interaction between clumping factor a and host vwf |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041789/ https://www.ncbi.nlm.nih.gov/pubmed/33846500 http://dx.doi.org/10.1038/s42003-021-01986-6 |
work_keys_str_mv | AT viljoenalbertus staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT vielafelipe staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT mathelieguinletmarion staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT missiakasdominique staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT pietrocolagiampiero staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT spezialepietro staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf AT dufreneyvesf staphylococcusaureusvwfbindingproteintriggersastronginteractionbetweenclumpingfactoraandhostvwf |