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β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC

Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural or...

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Autores principales: Barbu, E. Magda, Ganesh, Vannakambadi K., Gurusiddappa, Shivasankarappa, Mackenzie, R. Chris, Foster, Timothy J., Sudhof, Thomas C., Höök, Magnus
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800189/
https://www.ncbi.nlm.nih.gov/pubmed/20090838
http://dx.doi.org/10.1371/journal.ppat.1000726
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author Barbu, E. Magda
Ganesh, Vannakambadi K.
Gurusiddappa, Shivasankarappa
Mackenzie, R. Chris
Foster, Timothy J.
Sudhof, Thomas C.
Höök, Magnus
author_facet Barbu, E. Magda
Ganesh, Vannakambadi K.
Gurusiddappa, Shivasankarappa
Mackenzie, R. Chris
Foster, Timothy J.
Sudhof, Thomas C.
Höök, Magnus
author_sort Barbu, E. Magda
collection PubMed
description Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural organization with multiple domains adopting characteristic IgG-like folds. The identified microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) belong to this subfamily, as does SdrC from S. aureus. However, an interactive host ligand for the putative MSCRAMM SdrC was not previously identified. We have screened a phage display peptide library and identified a peptide sequence found in β-neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the β-neurexin 1 exodomain binds SdrC with high affinity and specificity. Furthermore, expression of SdrC on bacteria greatly enhances microbial adherence to cultured mammalian cells expressing β-neurexin on their surface. Taken together, our experimental results demonstrate that β-neurexin is a ligand for SdrC. This interaction involves a specific sequence located in the N-terminal region of the mammalian protein and the N(2)N(3) domain of the MSCRAMM. The fact that these two proteins interact when expressed on the appropriate cells demonstrates the functionality of the interaction. Possible implications of this interaction are discussed.
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spelling pubmed-28001892010-01-21 β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC Barbu, E. Magda Ganesh, Vannakambadi K. Gurusiddappa, Shivasankarappa Mackenzie, R. Chris Foster, Timothy J. Sudhof, Thomas C. Höök, Magnus PLoS Pathog Research Article Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural organization with multiple domains adopting characteristic IgG-like folds. The identified microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) belong to this subfamily, as does SdrC from S. aureus. However, an interactive host ligand for the putative MSCRAMM SdrC was not previously identified. We have screened a phage display peptide library and identified a peptide sequence found in β-neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the β-neurexin 1 exodomain binds SdrC with high affinity and specificity. Furthermore, expression of SdrC on bacteria greatly enhances microbial adherence to cultured mammalian cells expressing β-neurexin on their surface. Taken together, our experimental results demonstrate that β-neurexin is a ligand for SdrC. This interaction involves a specific sequence located in the N-terminal region of the mammalian protein and the N(2)N(3) domain of the MSCRAMM. The fact that these two proteins interact when expressed on the appropriate cells demonstrates the functionality of the interaction. Possible implications of this interaction are discussed. Public Library of Science 2010-01-15 /pmc/articles/PMC2800189/ /pubmed/20090838 http://dx.doi.org/10.1371/journal.ppat.1000726 Text en Barbu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Barbu, E. Magda
Ganesh, Vannakambadi K.
Gurusiddappa, Shivasankarappa
Mackenzie, R. Chris
Foster, Timothy J.
Sudhof, Thomas C.
Höök, Magnus
β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title_full β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title_fullStr β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title_full_unstemmed β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title_short β-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
title_sort β-neurexin is a ligand for the staphylococcus aureus mscramm sdrc
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800189/
https://www.ncbi.nlm.nih.gov/pubmed/20090838
http://dx.doi.org/10.1371/journal.ppat.1000726
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