Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2

Sreedam C. Das, Rodrigo A.V. Morales, Jeffrey Seow, Bankala Krishnarjuna, Ravindu Dissanayake, Robin F. Anders, Christopher A. Macraild, Raymond S. Norton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C-terminal region of MSP2, a construct corresponding to this domain, MSP2172-221, was designed. NMR studies indicate that many residues in MSP2172-221 interact with DPC micelles, including some in epitopes recognised by C-terminal-specific monoclonal antibodies, but, in contrast to the MSP2 N-terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172-221 is antigenically similar to full-length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172-221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates. 

Original languageEnglish
Pages (from-to)649–2662
Number of pages14
JournalFEBS Journal
Volume284
Issue number16
DOIs
Publication statusPublished - 2017

Keywords

  • Antigenicity
  • Lipid interaction
  • Liposome
  • Malaria
  • Merozoite surface protein 2

Cite this

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title = "Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2",
abstract = "Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C-terminal region of MSP2, a construct corresponding to this domain, MSP2172-221, was designed. NMR studies indicate that many residues in MSP2172-221 interact with DPC micelles, including some in epitopes recognised by C-terminal-specific monoclonal antibodies, but, in contrast to the MSP2 N-terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172-221 is antigenically similar to full-length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172-221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates. ",
keywords = "Antigenicity, Lipid interaction, Liposome, Malaria, Merozoite surface protein 2",
author = "Das, {Sreedam C.} and Morales, {Rodrigo A.V.} and Jeffrey Seow and Bankala Krishnarjuna and Ravindu Dissanayake and Anders, {Robin F.} and Macraild, {Christopher A.} and Norton, {Raymond S.}",
year = "2017",
doi = "10.1111/febs.14135",
language = "English",
volume = "284",
pages = "649–2662",
journal = "FEBS Journal",
issn = "1742-464X",
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Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2. / Das, Sreedam C.; Morales, Rodrigo A.V.; Seow, Jeffrey; Krishnarjuna, Bankala; Dissanayake, Ravindu; Anders, Robin F.; Macraild, Christopher A.; Norton, Raymond S.

In: FEBS Journal, Vol. 284, No. 16, 2017, p. 649–2662.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Lipid interactions modulate the structural and antigenic properties of the C-terminal domain of the malaria antigen merozoite surface protein 2

AU - Das, Sreedam C.

AU - Morales, Rodrigo A.V.

AU - Seow, Jeffrey

AU - Krishnarjuna, Bankala

AU - Dissanayake, Ravindu

AU - Anders, Robin F.

AU - Macraild, Christopher A.

AU - Norton, Raymond S.

PY - 2017

Y1 - 2017

N2 - Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C-terminal region of MSP2, a construct corresponding to this domain, MSP2172-221, was designed. NMR studies indicate that many residues in MSP2172-221 interact with DPC micelles, including some in epitopes recognised by C-terminal-specific monoclonal antibodies, but, in contrast to the MSP2 N-terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172-221 is antigenically similar to full-length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172-221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates. 

AB - Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C-terminal region of MSP2, a construct corresponding to this domain, MSP2172-221, was designed. NMR studies indicate that many residues in MSP2172-221 interact with DPC micelles, including some in epitopes recognised by C-terminal-specific monoclonal antibodies, but, in contrast to the MSP2 N-terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172-221 is antigenically similar to full-length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172-221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates. 

KW - Antigenicity

KW - Lipid interaction

KW - Liposome

KW - Malaria

KW - Merozoite surface protein 2

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U2 - 10.1111/febs.14135

DO - 10.1111/febs.14135

M3 - Article

VL - 284

SP - 649

EP - 2662

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

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