Fig. 3

Structural transitions of complement proteins upon MAC assembly. a Molecular model of complement proteins that interact with C5b (gray). * indicates uneven lengths of TMH regions of C6 (blue), C7 (orange), and C8β (magenta). b Coulombic surface potential (from red -10 kcal/mol*e to blue + 10 kcal/mol*e) of atomic models for C5b, C6, C7, C8 and two adjacent C9 monomers viewed from the convex face of the barrel (same view as in a). Dotted line highlights a patch of positively charged residues within the membrane-interacting regions of C6, C7, and C8. Transmembrane regions of C8 and C9 are indicated (TM). * indicates the same region as in a. c Coulombic surface potential representation for MACPF interaction interfaces of complement proteins. d Superposition of the MAC form of C6 (colored) and C6 from the soluble C5b6 crystal structure lacking TMH residues (PDB: 4A5W; gray). Rotations in C6 TSP (cyan), LDL (light green), and EGF (dark green) domains accompany movement of CH3 latch (magenta) and unfurling of transmembrane β-hairpins. e Genetic variants identified in AMD patients mapped on the C9 structure. Mutations reported to decrease polymerization are cyan, those reported to cause spontaneous self-polymerization are orange³⁰