Defining the intermedilysin-human CD59 interaction.

摘要

Intermedilysin (ILY) initiates its cytolytic mechanism by binding to a cellular receptor, human CD59 (hCD59). Binding of ILY to hCD59 initiates a series of conformational changes within the toxin that result in the conversion of the soluble monomer into an oligomeric membrane embedded pore complex. In the current study the specific amino acid residues composing the complementary binding sites on ILY and hCD59 have been identified. These studies show the binding interface to be rich in aromatic residues. The hCD59 residues involved in binding to ILY were also involved in protection from complement-mediated cell lysis suggesting significant overlap in the ILY and C8alpha and C9 binding sites. Those residues shown to contribute to the ILY binding site for hCD59 were also conserved in vaginolysin (VLY), the only other CDC shown to specifically bind hCD59. Finally, these studies show that the affinity of the ILY-hCD59 interaction is relatively low and that the high affinity interaction with the cell surface is mediated by the membrane insertion of the domain 4 loops L1-L3.