1.C.12.1.13
Intermedilysin of 532 aas and 1 N-terminal TMS, ILY or Ply.  It binds to membranes containing the human protein CD59 but forms pores only if the membrane contains sufficient cholesterol (Heuck et al. 2007).  CD59 is required for the specific coordination of intermedilysin (ILY) monomers and for triggering collapse of an oligomeric prepore. Movement of Domain 2 with respect to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while the role of cholesterol may be limited to insertion of the TMSs (Boyd et al. 2016). The pore-forming regions are initially folded up on the surfaces of the soluble precursors. To create the transmembrane pores, these regions must extend and refold into membrane-inserted beta-barrels (Tilley and Saibil 2006). The intermedilysin cytolytic activity depends on heparan sulfates and the membrane composition (Drabavicius and Daelemans 2021).