Fig. 2: CDC, CDCL, and complement C8α and C9 structures structures.

a Crystal structures of the archetype CDC perfringolysin (PFO) from Clostridium perfringens¹ (PDB: 1PFO), the EaCDCL^L (PDB: 8G33) and EaCDCL^S (PDB: 8G32) proteins from E. anophelis⁷ and complement proteins C8α⁴⁷ (PDB: (2QQH) and C9⁴⁸ (PDB: 6CXO). The BfCDCL^L and BfCDCL^S structures were obtained from the AlphaFold2 database¹⁰ (AlphaFold2 designations BF1276 and BF1275, respectively). The cognate α-helical bundles are shown that refold into the transmembrane β-hairpins 1 (TMH1, magenta) and 2 (TMH2, yellow), which form the β-barrel pore in all structures. The PFO β-tongue is shown in blue, whereas the analogous regions are not resolved in the crystal structures of EaCDCL^{L (7)} and EaCDCL^S (solved herein), but the bounding residues are shown as blue space-filled atoms. The AlphaFold2 models of BfCDCL^L and BfCDCL^S do not show their SpII signal peptides. Whereas the analogous regions to the CDC β-tongue are not visualized in the crystal structures of the EaCDCLs, the AlphaFold2 models of the BfCDCLs show the analogous regions as folded (ribbons colored in blue). However, the pLDDT confidence metric falls below 50, and the PAE metric is high in this region (Supplementary Fig. 3, and b, below), suggesting that the regions structures are unreliable. The YGR and GG motifs common to the CDCs and CDCLs⁷ are shown in cyan and orange space-filled atoms, respectively. Arg70 and Arg62 are shown in tan atoms in BfCDCL^L and BfCDCL^S, respectively. The GG motif largely lays behind the YGR motif atoms in the image. The core C9 structure resembles that of the CDCLs domains 1–3 (shown in gray). The C9 ancillary domains are shown in color (EGF, epidermal growth factor: blue, TSP1, thrombospondin type 1: purple and LDLRA, low-density lipoprotein receptor Type A: brown), which do not correspond to any structures in the CDCL^S. b Shown are the pLDDT values colored onto the AlphaFold2 models of BfCDCL^L and BfCDCL^S from the AlphaFold2 structural database¹⁰.