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Related Experiment Videos

Coevolutionary patterns in plasminogen activation.

Inna P Gladysheva1, Ryan B Turner, Irina Y Sazonova

  • 1Cardiovascular Biology Laboratory, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 25, 2003
PubMed
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Bacterial plasminogen activators (PAs) have limited ability to activate animal plasminogen (Pg). Mutations altering complementarity between streptokinase (SK) and plasminogen (Pg) can change SK

Area of Science:

  • Molecular biology
  • Biochemistry
  • Evolutionary biology

Background:

  • Plasminogen (Pg) activators (PAs) are crucial for physiological processes like clot dissolution and cell migration.
  • Pathogenic bacteria utilize bacterial PAs (e.g., streptokinase) to exploit the host's Pg system for infection.
  • A significant difference exists in the substrate specificity of bacterial PAs towards animal Pgs compared to animal PAs.

Purpose of the Study:

  • To investigate how mutations in bacterial PAs affect their ability to activate diverse animal Pgs.
  • To understand the evolutionary interplay between bacterial PAs and host Pg systems.

Main Methods:

  • Comparative sequence analysis of bacterial PAs and animal plasmin.
  • Mutational analysis of streptokinase (SK) to assess its interaction with plasminogen (Pg).

Related Experiment Videos

  • Analysis of intermolecular complementarity at protein-protein interaction sites.

    • Main Results:

    • Mutations in bacterial PAs, specifically SK, can significantly alter their spectrum of activity against animal Pgs.
    • Sites in plasmin targeted by SK show preferential mutation in animal Pgs compared to non-target homologues.
    • SK interaction sites crucial for activating human Pg are highly conserved, suggesting evolutionary pressure.

    Conclusions:

    • The restricted activity of bacterial PAs against animal Pgs is influenced by intermolecular complementarity.
    • Evolutionary adaptations in both bacterial PAs and animal Pgs shape their interaction dynamics.
    • Modulation of complementarity at SK-Pg contact sites represents a key battleground in host-pathogen co-evolution.