Human CD59 Is a Receptor for the Cholesterol-Dependent Cytolysin Intermedilysin

Nat Struct Mol Biol. 2004 Dec;11(12):1173-8. doi: 10.1038/nsmb862. Epub 2004 Nov 14.


Cholesterol is believed to serve as the common receptor for the cholesterol-dependent cytolysins (CDCs). One member of this toxin family, Streptococcus intermedius intermedilysin (ILY), exhibits a narrow spectrum of cellular specificity that is seemingly inconsistent with this premise. We show here that ILY, via its domain 4 structure, binds to the glycosyl-phosphatidylinositol-linked membrane protein human CD59 (huCD59). CD59 is an inhibitor of the membrane attack complex of human complement. ILY specifically binds to huCD59 via residues that are the binding site for the C8alpha and C9 complement proteins. These studies provide a new model for the mechanism of cellular recognition by a CDC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / toxicity*
  • Bacteriocins
  • Binding Sites
  • CD59 Antigens / metabolism*
  • Cell Line
  • Cholesterol / metabolism*
  • Erythrocytes / drug effects
  • Erythrocytes / pathology
  • Glycosylation
  • Humans
  • Mice
  • Models, Molecular
  • Protein Structure, Tertiary
  • Rabbits
  • Substrate Specificity
  • Trypsin / metabolism


  • Bacterial Proteins
  • Bacteriocins
  • CD59 Antigens
  • intermedilysin protein, Streptococcus intermedius
  • Cholesterol
  • Trypsin