title: EGCG disaggregates amyloid-like fibrils formed by Plasmodium falciparum merozoite surface protein 2.
abstract: Merozoite surface protein 2 (MSP2), one of the most abundant proteins on the surface of Plasmodium falciparum merozoites, is a promising malaria vaccine candidate. MSP2 is intrinsically unstructured and forms amyloid-like fibrils in solution. As this propensity of MSP2 to form fibrils in solution has the potential to impede its development as a vaccine candidate, finding an inhibitor that inhibits fibrillogenesis may enhance vaccine development. We have shown previously that EGCG inhibits the formation of MSP2 fibrils. Here we show that EGCG can alter the β-sheet-like structure of the fibril and disaggregate pre-formed fibrils of MSP2 into soluble oligomers. The fibril remodelling effects of EGCG and other flavonoids were characterised using Thioflavin T fluorescence assays, electron microscopy and other biophysical methods.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Indu R
authors.initials: IR
authors.lastname: Chandrashekaran
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Adda
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Macraild
authors.forename: Robin F
authors.initials: RF
authors.lastname: Anders
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Norton
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000187:drug effects* / Q000648:ultrastructure; D055592:Biophysical Phenomena; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017780:Malaria Vaccines / Q000737:chemistry; D052940:Merozoites / Q000737:chemistry / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000187:drug effects*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D015800:Protozoan Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D000682:Amyloid; D000953:Antigens, Protozoan; D005419:Flavonoids; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; D002392:Catechin; C045651:epigallocatechin gallate