Abstract
Merozoite surface protein 2 (MSP2) from the human malaria parasite Plasmodium falciparum is expressed as a GPI‐anchored protein on the merozoite surface. It has been implicated in the process of erythrocyte invasion and is a leading vaccine candidate. MSP2 is an intrinsically unstructured protein (IUP), and recombinant MSP2 forms amyloid‐like fibrils upon storage. We have examined synthetic peptides corresponding to sequences in the conserved N‐terminal region of MSP2 for the presence of local structure and the ability to form fibrils related to those formed by full‐length MSP2. In a 25‐residue peptide corresponding to the entire N‐terminal region of mature MSP2, structures calculated from NMR data show the presence of nascent helical and turn‐like structures. An 8‐residue peptide from the central region of the N‐terminal domain (residues 8–15) also formed a turn‐like structure. Both peptides formed fibrils that were similar but not identical to the amyloid‐like fibrils formed by full‐length MSP2. Notably, the fibrils formed by the peptides bound both Congo Red and Thioflavin T, whereas the fibrils formed by full‐length MSP2 bound only Congo Red. The propensity of peptides from the N‐terminal conserved region of MSP2 to form amyloid‐like fibrils makes it likely that this region contributes to fibril formation by the full‐length protein. Thus, in contrast to the more common pathway of amyloid formation by structured proteins, which proceeds via partially unfolded intermediates that then undergo β‐aggregation, MSP2 is an example of a largely unstructured protein with at least one small structured region that has an important role in fibril formation. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.