Fig. 3: Cryo-EM structure of the classical and lectin pathway convertase in complex with substrate C3.
From: Structural insights into C3 convertase activity of the classical pathway of complement
a Cryo-EM density map in two 180°-rotated orientations of C4b2b-C3 colored by local resolution from high (blue) to low (red), and cartoon representation of the C4b2b-C3 model built in this map. C4b2b colors are as in Fig. 2 with C3 shown in orange. b–d Structural changes in the VWA domain upon conversion from C4b2 to C4b2b using the C4b2b-C3 structure. Helix αL of the C2 pro-peptide in C4b2 is shown in pink and VWA domains of C4b2b in green and C4b2 in light yellow. e Domain reorientations in C4b2b upon substrate C3 binding with C3-bound and unbound convertases superposed using the C4b β-chain. C4b and C2b of C4b2b-C3 shown in blue and in green, respectively, with those of C4b2b in faded colors. Arrows denote the domain reorientations going from C4b2b to C4b2b-C3. f Domain reorientations in C3 upon binding to the convertase with C3 of C4b2b-C3 in orange and unbound C3 (PDB 2A73) in grey; molecules superposed using the MG1 and MG5 domains. g Surface representations of C4b2b (left) and C3 (right) from the C4b2b-C3 complex showing the contact sites. Proteins are colored as before with contact sites shown in the color of the opposing surface.
