Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2

Christopher Andrew MacRaild, Milan Zachrdla, Dean W Andrew, Bankala Krishnarjuna, Jiri Novacek, Lukas Zidek, Vladimir Sklenar, Jonathan S Richards, James G Beeson, Robin Fredric Anders, Raymond Stanley Norton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- And C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.
Original languageEnglish
Article numbere0119899
Number of pages18
JournalPLoS ONE
Volume10
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

MacRaild, Christopher Andrew ; Zachrdla, Milan ; Andrew, Dean W ; Krishnarjuna, Bankala ; Novacek, Jiri ; Zidek, Lukas ; Sklenar, Vladimir ; Richards, Jonathan S ; Beeson, James G ; Anders, Robin Fredric ; Norton, Raymond Stanley. / Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2. In: PLoS ONE. 2015 ; Vol. 10, No. 3.
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abstract = "Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- And C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.",
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Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2. / MacRaild, Christopher Andrew; Zachrdla, Milan; Andrew, Dean W; Krishnarjuna, Bankala; Novacek, Jiri; Zidek, Lukas; Sklenar, Vladimir; Richards, Jonathan S; Beeson, James G; Anders, Robin Fredric; Norton, Raymond Stanley.

In: PLoS ONE, Vol. 10, No. 3, e0119899, 2015.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2

AU - MacRaild, Christopher Andrew

AU - Zachrdla, Milan

AU - Andrew, Dean W

AU - Krishnarjuna, Bankala

AU - Novacek, Jiri

AU - Zidek, Lukas

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AU - Richards, Jonathan S

AU - Beeson, James G

AU - Anders, Robin Fredric

AU - Norton, Raymond Stanley

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