A partially structured region of a largely unstructured protein,Plasmodium falciparummerozoite surface protein 2 (MSP2), forms amyloid-like fibrils
| Autor: | David W. Keizer, Raymond S. Norton, Christopher G. Adda, Michael Rizkalla, Robin F. Anders, Xiaodong Yang, Matthew A. Perugini, Vince J. Murphy, David C. Jackson |
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| Rok vydání: | 2007 |
| Předmět: |
Amyloid
Circular dichroism Magnetic Resonance Spectroscopy Plasmodium falciparum Protozoan Proteins Antigens Protozoan Peptide macromolecular substances Biology Fibril Biochemistry Protein Structure Secondary chemistry.chemical_compound Protein structure Structural Biology parasitic diseases Drug Discovery Animals Amino Acid Sequence Merozoite surface protein Molecular Biology Peptide sequence Pharmacology chemistry.chemical_classification Circular Dichroism Organic Chemistry General Medicine Peptide Fragments Congo red Solutions Microscopy Electron chemistry Biophysics Molecular Medicine Thioflavin |
| Zdroj: | Journal of Peptide Science. 13:839-848 |
| ISSN: | 1099-1387 1075-2617 |
| DOI: | 10.1002/psc.910 |
| Popis: | 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 beta-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. |
| Databáze: | OpenAIRE |
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