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

PLoS One. 2015 Mar 25;10(3):e0121764. doi: 10.1371/journal.pone.0121764. eCollection 2015.

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 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Phosphopyruvate Hydratase / metabolism*
  • Plasminogen / metabolism*
  • Protein Binding
  • Protein Conformation
  • Streptococcus pyogenes / metabolism*

Substances

  • Bacterial Proteins
  • Plasminogen
  • streptococcal surface enolase
  • Phosphopyruvate Hydratase

Associated data

  • PDB/3ZLF
  • PDB/3ZLG
  • PDB/3ZLH

Grants and funding

This work is supported by the National Health and Medical Research Council (NHMRC; APP565526). BK and MJW are NHMRC Research Fellows. JCW is an ARC Federation Fellow and Honorary NHMRC Principal Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.