Structural and Functional Insights into the Malaria Parasite Moving Junction Complex
Figure 2
Structure of PfAMA1 complexed with PfRON2-derived peptides.
(A) Top - Co-crystal structures of PfAMA1 (blue surface) with PfRON2sp1 (orange) and PfRON2sp2 (grey), show a disulfide-anchored U-shaped conformation in the apical groove of PfAMA1. Bottom - Electron density map (orange) for PfRON2sp1 contoured at 1.0 σ, highlighting well ordered density from the N-terminal helix, through the cystine loop, to the C-terminal coil. (B) Notable changes in the structure of PfAMA1 between the apo structure (green; PDB ID 1Z40) and the PfAMA1-PfRON2sp1 co-structure (blue-orange) as observed from a side view. Box 1 - The DII loop of apo PfAMA1 is ejected from the apical groove during binding to PfRON2sp1, leaving room for the PfRON2sp1 N-terminal helix to occupy the space vacated by the DII loop helix. Box 2 - The β-strands of the PfRON2sp1 cystine loop order a PfAMA1 surface loop, generating a contiguous three-stranded β-sheet. (C) In the region of the PfRON2sp1 N-terminal helix, there is notable structural mimicry to the PfAMA1 apo DII loop, including several conserved residues, and a conserved hydrogen bonding network incorporating three buried water molecules. (D) Arg2041, specific to P. falciparum, fits snugly into a deep pocket in the surface of PfAMA1 and is stabilized through a complex network of seven hydrogen bonds.