Role of the Helical Structure of the N-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 2 in Fibril Formation and Membrane Interaction
- Author(s)
- Zhang, XC; Adda, CG; Low, A; Zhang, JH; Zhang, W; Sun, HB; Tu, XM; Anders, RF; Norton, RS;
- Details
- Publication Year 2012-02-21,Volume 51,Issue #7,Page 1380-1387
- Journal Title
- BIOCHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Merozoite surface protein 2 (MSP2), an abundant glycosylphosphatidylinositol-anchored protein on the surface of Plasmodium falciparum merozoites, is a promising malaria vaccine candidate. MSP2 is intrinsically disordered and forms amyloid-like fibrils in solution under physiological conditions. The 25 N-terminal residues (MSP2(1-25)) play an important role in both fibril formation and membrane binding of the full-length protein. In this study, the fibril formation and solution structure of MSP2(1-25) in the membrane mimetic solvents sodium dodecyl sulfate (SDS), dodecylphosphocholine (DPC), and trifluoroethanol (TFE) have been investigated by transmission electronic microscopy, turbidity, thioflavin T fluorescence, circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy. Turbidity data showed that the aggregation of MSP2(1-25) was suppressed in the presence of membrane mimetic solvents. CD spectra indicated that helical structure in MSP2(1-25) was stabilized in SDS and DPC micelles and in high concentrations of TFE. The structure of MSP2(1-25) in 50% aqueous TFE, determined using NMR, showed that the peptide formed an amphipathic helix encompassing residues 10-24. Low concentrations of TFE favored partially folded helical conformations, as demonstrated by CD and NMR, and promoted MSP2(1-25) fibril formation. Our data suggest that partially folded helical conformations of the N-terminal region of MSP2 are on the pathway to amyloid fibril formation, while higher degrees of helical structure stabilized by high concentrations of TFE or membrane mimetics suppress self-association and thus inhibit fibril formation. The roles of the induced helical conformations in membrane interactions are also discussed.
- Publisher
- AMER CHEMICAL SOC
- Keywords
- FIBRILLIZATION IN-VITRO; AMYLOID-LIKE FIBRILS; ALPHA-SYNUCLEIN; BACKBONE DYNAMICS; CHEMICAL-SHIFTS; NMR; PEPTIDE; AGGREGATION; MALARIA; FORMS
- Research Division(s)
- Structural Biology
- Publisher's Version
- https://doi.org/10.1021/bi201880s
- Terms of Use/Rights Notice
- Copyright © 2012 American Chemical Society
Creation Date: 2012-02-21 12:00:00