Specificity between SporoAMA1 and SporoRON2-D3 is achieved through interactions within both the cysteine loop and the connecting coil.

Abstract

<p>A<b>.</b> Apical view of sporoAMA1 (green surface) bound to sporoRON2-D3 (gold cartoon) (left), showing conservation of the overall AMA1/RON2 binding paradigm with generic AMA1 (purple surface) – generic RON2 synthetic peptide (sp; green cartoon) (right; PDB 2Y8T). Note that the extreme C-terminal portion of the sporoRON2 peptide is disordered as a result of its relatively “early” exit from the stabilizing environment of the hydrophobic groove and therefore is not resolved in this structure. B. Cysteine loop interactions clearly differ between sporoAMA1-sporoRON2-D3 (left) and generic AMA1-generic RON2sp (right). Hydrogen bonds shown as dotted black lines. Colored as in (A). C. Additional specificity is gained through interactions with sporoAMA1 (green surface) or generic AMA1 (purple surface) and the RON2 coil that connects the N-term helix to the cysteine loop. Central groove residue (sporoAMA1 Ser252 or generic AMA1 Tyr230) and generic AMA1 groove residue Met233 colored dark grey. Beta-hairpin loop 3 and variable loop 4 colored light grey. Side chains of sporoRON2-D3 (gold cartoon) and generic RON2sp (green cartoon) involved in specificity shown as sticks.</p