EGCG disaggregates amyloid-like fibrils formed by Plasmodium falciparum merozoite surface protein 2

Indu Chandrashekaran, Christopher Adda, Christopher MacRaild, Robin Anders, Raymond Norton

Research output: Contribution to journalArticleResearchpeer-review

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 beta-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. (C) 2011 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)153 - 157
Number of pages5
JournalArchives of Biochemistry and Biophysics
Volume513
Issue number2
DOIs
Publication statusPublished - 2011

Cite this

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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 beta-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. (C) 2011 Elsevier Inc. All rights reserved.",
author = "Indu Chandrashekaran and Christopher Adda and Christopher MacRaild and Robin Anders and Raymond Norton",
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language = "English",
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}

EGCG disaggregates amyloid-like fibrils formed by Plasmodium falciparum merozoite surface protein 2. / Chandrashekaran, Indu; Adda, Christopher; MacRaild, Christopher; Anders, Robin; Norton, Raymond.

In: Archives of Biochemistry and Biophysics, Vol. 513, No. 2, 2011, p. 153 - 157.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - EGCG disaggregates amyloid-like fibrils formed by Plasmodium falciparum merozoite surface protein 2

AU - Chandrashekaran, Indu

AU - Adda, Christopher

AU - MacRaild, Christopher

AU - Anders, Robin

AU - Norton, Raymond

PY - 2011

Y1 - 2011

N2 - 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 beta-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. (C) 2011 Elsevier Inc. All rights reserved.

AB - 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 beta-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. (C) 2011 Elsevier Inc. All rights reserved.

UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0003986111002608

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DO - 10.1016/j.abb.2011.07.008

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JO - Archives of Biochemistry and Biophysics

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