Interactions between membrane-bound streptococcal alpha-enolase and human plasminogen captured through...

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Invasive *Streptococcus pyogenes* utilizes human plasminogen (hPg) for pathogenesis.
• Surface proteins like enolase (SEn) bind hPg, aiding bacterial dissemination.
• The mechanism of SEn surface translocation and hPg binding is poorly understood.

Purpose of the Study:

• To elucidate the mechanism of enolase (SEn) translocation to the bacterial surface.
• To investigate how SEn binds human plasminogen (hPg).
• To understand how SEn influences hPg activation.

Main Methods:

• Cryogenic-electron microscopy (cryo-EM) of SEn in liposomes.
• Modeling of SEn within a lipid microvesicle (MV) environment.
• Analysis of SEn-hPg interactions and hPg activation.

Main Results:

• SEn is exported via lipid microvesicles (MVs).
• Cryo-EM revealed SEn's orientation within MVs, with subunits exposed extracellularly.
• SEn binding to hPg does not induce conformational changes but enhances activation via tissue-type plasminogen activator (tPA).

Conclusions:

• SEn utilizes MVs for surface display, a novel translocation pathway.
• SEn promotes hPg activation primarily by facilitating the SEn-tPA interaction.
• This MV-mediated mechanism contributes to *S. pyogenes* pathogenesis independent of hPg conformational changes.