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Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase

Group A Streptococcus (GAS) is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen). Streptococcal surface enolase (SEN) is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell,...

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Autores principales: Cork, Amanda J., Ericsson, Daniel J., Law, Ruby H. P., Casey, Lachlan W., Valkov, Eugene, Bertozzi, Carlo, Stamp, Anna, Jovcevski, Blagojce, Aquilina, J. Andrew, Whisstock, James C., Walker, Mark J., Kobe, Bostjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373793/
https://www.ncbi.nlm.nih.gov/pubmed/25807546
http://dx.doi.org/10.1371/journal.pone.0121764
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author Cork, Amanda J.
Ericsson, Daniel J.
Law, Ruby H. P.
Casey, Lachlan W.
Valkov, Eugene
Bertozzi, Carlo
Stamp, Anna
Jovcevski, Blagojce
Aquilina, J. Andrew
Whisstock, James C.
Walker, Mark J.
Kobe, Bostjan
author_facet Cork, Amanda J.
Ericsson, Daniel J.
Law, Ruby H. P.
Casey, Lachlan W.
Valkov, Eugene
Bertozzi, Carlo
Stamp, Anna
Jovcevski, Blagojce
Aquilina, J. Andrew
Whisstock, James C.
Walker, Mark J.
Kobe, Bostjan
author_sort Cork, Amanda J.
collection PubMed
description Group A Streptococcus (GAS) is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen). Streptococcal surface enolase (SEN) is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen) on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen) binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SEN(K312A) and SEN(K362A) is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen) to its binding sites, leading to more efficient plasmin(ogen) binding and activation.
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spelling pubmed-43737932015-03-27 Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase Cork, Amanda J. Ericsson, Daniel J. Law, Ruby H. P. Casey, Lachlan W. Valkov, Eugene Bertozzi, Carlo Stamp, Anna Jovcevski, Blagojce Aquilina, J. Andrew Whisstock, James C. Walker, Mark J. Kobe, Bostjan PLoS One Research Article Group A Streptococcus (GAS) is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen). Streptococcal surface enolase (SEN) is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen) on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen) binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SEN(K312A) and SEN(K362A) is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen) to its binding sites, leading to more efficient plasmin(ogen) binding and activation. Public Library of Science 2015-03-25 /pmc/articles/PMC4373793/ /pubmed/25807546 http://dx.doi.org/10.1371/journal.pone.0121764 Text en © 2015 Cork 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
Cork, Amanda J.
Ericsson, Daniel J.
Law, Ruby H. P.
Casey, Lachlan W.
Valkov, Eugene
Bertozzi, Carlo
Stamp, Anna
Jovcevski, Blagojce
Aquilina, J. Andrew
Whisstock, James C.
Walker, Mark J.
Kobe, Bostjan
Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title_full Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title_fullStr Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title_full_unstemmed Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title_short Stability of the Octameric Structure Affects Plasminogen-Binding Capacity of Streptococcal Enolase
title_sort stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373793/
https://www.ncbi.nlm.nih.gov/pubmed/25807546
http://dx.doi.org/10.1371/journal.pone.0121764
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