Structure of the lectin regulatory domain of the cholesterol-dependent cytolysin lectinolysin reveals the basis for its lewis antigen specificity

Structure. 2012 Feb 8;20(2):248-58. doi: 10.1016/j.str.2011.11.017.


The cholesterol-dependent cytolysins (CDCs) punch holes in target cell membranes through a highly regulated process. Streptococcus mitis lectinolysin (LLY) exhibits another layer of regulation with a lectin domain that enhances the pore-forming activity of the toxin. We have determined the crystal structures of the lectin domain by itself and in complex with various glycans that reveal the molecular basis for the Lewis antigen specificity of LLY. A small-angle X-ray scattering study of intact LLY reveals the molecule is flat and elongated with the lectin domain oriented so that the Lewis antigen-binding site is exposed. We suggest that the lectin domain enhances the pore-forming activity of LLY by concentrating toxin molecules at fucose-rich sites on membranes, thus promoting the formation of prepore oligomers on the surface of susceptible cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Fucose / chemistry
  • Hydrogen Bonding
  • Lectins / chemistry*
  • Lewis Blood Group Antigens / chemistry*
  • Models, Molecular
  • Pore Forming Cytotoxic Proteins / chemistry*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Scattering, Small Angle
  • Streptococcus mitis*
  • X-Ray Diffraction


  • Bacterial Proteins
  • Lectins
  • Lewis Blood Group Antigens
  • Lewis Y antigen
  • Pore Forming Cytotoxic Proteins
  • Fucose

Associated data

  • PDB/3LE0
  • PDB/3LEG
  • PDB/3LEI