Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase

Amanda J Cork, Daniel J Ericsson, Ruby H P Law, Lachlan W Casey, Eugene Valkov, Carlo Bertozzi, Anna Stamp, Blagojce Jovcevski, J Andrew Aquilina, James C Whisstock, Mark J Walker, Bostjan Kobe

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Abstract

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 alpha-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 SENK312A and SENK362A 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.
Original languageEnglish
Article numbere0121764
Number of pages18
JournalPLoS ONE
Volume10
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

Cork, A. J., Ericsson, D. J., Law, R. H. P., Casey, L. W., Valkov, E., Bertozzi, C., ... Kobe, B. (2015). Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase. PLoS ONE, 10(3), [e0121764]. https://doi.org/10.1371/journal.pone.0121764
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. In: PLoS ONE. 2015 ; Vol. 10, No. 3.
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abstract = "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 alpha-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 SENK312A and SENK362A 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.",
author = "Cork, {Amanda J} and Ericsson, {Daniel J} and Law, {Ruby H P} and Casey, {Lachlan W} and Eugene Valkov and Carlo Bertozzi and Anna Stamp and Blagojce Jovcevski and Aquilina, {J Andrew} and Whisstock, {James C} and Walker, {Mark J} and Bostjan Kobe",
year = "2015",
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Cork, AJ, Ericsson, DJ, Law, RHP, Casey, LW, Valkov, E, Bertozzi, C, Stamp, A, Jovcevski, B, Aquilina, JA, Whisstock, JC, Walker, MJ & Kobe, B 2015, 'Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase', PLoS ONE, vol. 10, no. 3, e0121764. https://doi.org/10.1371/journal.pone.0121764

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.

In: PLoS ONE, Vol. 10, No. 3, e0121764, 2015.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase

AU - Cork, Amanda J

AU - Ericsson, Daniel J

AU - Law, Ruby H P

AU - Casey, Lachlan W

AU - Valkov, Eugene

AU - Bertozzi, Carlo

AU - Stamp, Anna

AU - Jovcevski, Blagojce

AU - Aquilina, J Andrew

AU - Whisstock, James C

AU - Walker, Mark J

AU - Kobe, Bostjan

PY - 2015

Y1 - 2015

N2 - 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 alpha-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 SENK312A and SENK362A 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.

AB - 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 alpha-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 SENK312A and SENK362A 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373793/pdf/pone.0121764.pdf

U2 - 10.1371/journal.pone.0121764

DO - 10.1371/journal.pone.0121764

M3 - Article

VL - 10

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e0121764

ER -