The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module

J Biol Chem. 2012 Nov 2;287(45):38178-89. doi: 10.1074/jbc.M112.376434. Epub 2012 Sep 12.


Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Bacterial Adhesion / genetics
  • Binding Sites / genetics
  • Carbohydrates / chemistry
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / microbiology
  • Carcinoma, Squamous Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Keratinocytes / microbiology
  • Models, Molecular
  • Mutation
  • Plasminogen / chemistry
  • Plasminogen / metabolism
  • Protein Binding
  • Protein Structure, Tertiary*
  • Scattering, Small Angle
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / metabolism*
  • Surface Plasmon Resonance
  • X-Ray Diffraction


  • Adhesins, Bacterial
  • Carbohydrates
  • Plasminogen

Associated data

  • PDB/4ES8
  • PDB/4ES9