Figure 2

Crystal structure to 1.2 Å resolution of 6D8 Fv bound to the 9-mer peptide MSP2_14–22. (A) Helical propensity of synthetic epitope-bearing peptides MSP2_11–23 and MSP2_14–22. Both peptides showed ellipticity at 190, 208 and 220 nm, consistent with some helical content in water, with the longer peptide having significantly greater tendency for helical conformation. (B) Crystal structure of MSP2_14–22 at the paratope cleft formed by the antibody CDRs. (C) MSP2_14–22 adopts a single turn of helix stabilized by hydrogen bonds with residues Asp31^H, Asp32^H, Val101^H and Asn38^L. In solution, Arg22 contacts residues Thr91^L and Asn92^L while the guanidine group of Arg23 of the peptide bends towards the N-terminus of the peptide, establishing critical hydrogen bonds with Asp32 in the VH chain and the carbonyl of Tyr16. (D) The structure of the lipid-bound form of MSP2_1–25²⁵ indicating the relative orientation of residues Try16, Arg21 and Arg22. The α-helical configuration of the lipid-bound MSP2_1–25 removes the backbone flexibility required for Arg22 to access Tyr16, which provides a structural rationale for the lack of binding of mAb 6D8 to MSP2 at the parasite membrane.