Fig. 5. Model for CDC pore formation and membrane lysis.

Soluble monomers (pink) bind target membranes through interactions with either cholesterol or cell surface receptors, such as CD59 (orange). Oligomerization of the membrane-bound subunits (green box) causes structural rearrangements that include a shift (blue arrow) of the amphipathic h-helix (pink cylinder), as captured in our cryoEM reconstruction. The early prepore, which extends 10 nm from the lipid bilayer, collapses to 8 nm and brings the charged face of the h-helix (blue and red circles) into contact with the membrane. The amphipathic h-helix disrupts the membrane, leading to the transition of helical bundles (HB1 and HB2) into membrane-piercing β-hairpins. For ILY, CD59 dissociates, as it is not part of the final pore. Though only three monomers are displayed, this process occurs for higher oligomer arc and ring-like pores¹⁴. Figure is based on ILY and PLY structures: PDBIDs 6ZD0, 1S3R⁵⁴, 4BIK¹⁷, 5CR6¹⁵, and 5LY6¹⁵; and EMD-4118¹⁵.