A partially structured region of a largely unstructured protein, Plasmodium falciparum merozoite surface protein 2 (MSP2), forms amyloid-like fibrils
Details
Publication Year 2007-12, Volume 13, Issue #12, Page 839-848
Journal Title
JOURNAL OF PEPTIDE SCIENCE
Publication Type
Journal Article
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 P-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 (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.
Publisher
JOHN WILEY & SONS LTD
Keywords
MEMBRANE ANTIGEN 1; NMR-SPECTROSCOPY; SELF-ASSOCIATION; TURN FORMATION; PEPTIDES; MALARIA; IMMUNIZATION; AGGREGATION; MICE; POLYMORPHISM
Publisher's Version
https://doi.org/10.1002/psc.910
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2007-12-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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