Identification of a plasminogen-binding motif in PAM, a bacterial surface protein

Mol Microbiol. 1995 Nov;18(3):569-78. doi: 10.1111/j.1365-2958.1995.mmi_18030569.x.


Surface-associated plasmin(ogen) may contribute to the invasive properties of various cells. Analysis of plasmin(ogen)-binding surface proteins is therefore of interest. The N-terminal variable regions of M-like (ML) proteins from five different group A streptococcal serotypes (33, 41, 52, 53 and 56) exhibiting the plasminogen-binding phenotype were cloned and expressed in Escherichia coli. The recombinant proteins all bound plasminogen with high affinity. The binding involved the kringle domains of plasminogen and was blocked by a lysine analogue, 6-aminohexanoic acid, indicating that lysine residues in the M-like proteins participate in the interaction. Sequence analysis revealed that the proteins contain common 13-16-amino-acid tandem repeats, each with a single central lysine residue. Experiments with fusion proteins and a 30-amino-acid synthetic peptide demonstrated that these repeats harbour the major plasminogen-binding site in the ML53 protein, as well as a binding site for the tissue-type plasminogen activator. Replacement of the lysine in the first repeat with alanine reduced the plasminogen-binding capacity of the ML53 protein by 80%. The results precisely localize the binding domain in a plasminogen surface receptor, thereby providing a unique ligand for the analysis of interactions between kringles and proteins with internal kringle-binding determinants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Base Sequence
  • Binding Sites
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Kringles
  • Lysine / analogs & derivatives
  • Lysine / antagonists & inhibitors
  • Molecular Sequence Data
  • Phenotype
  • Plasminogen / metabolism*
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Streptococcus pyogenes / chemistry*
  • Streptococcus pyogenes / genetics


  • Bacterial Proteins
  • Carrier Proteins
  • Recombinant Proteins
  • plasminogen-binding protein, bacteria
  • Plasminogen
  • Lysine