A partially structured region of a largely unstructured protein, Plasmodium falciparum merozoite surface protein 2 (MSP2), forms amyloid-like fibrils

Xiaodong Yang, Christopher G. Adda, David W. Keizer, Vince J. Murphy, Michael M. Rizkalla, Matthew A. Perugini, David C. Jackson, Robin F. Anders, Raymond S. Norton

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

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. Ina 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.

Original languageEnglish
Pages (from-to)839-848
Number of pages10
JournalJournal of Peptide Science
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

Keywords

  • Amyloid
  • Fibril
  • Malaria
  • NMR
  • Structure

Cite this