Merozoite Surface Protein 3 and Protection against Malaria in<i>Aotus nancymai</i>Monkeys

Hisaeda, Hajime; Saul, Allan; Reece, Joshua J.; Kennedy, Michael; Long, Carole A.; Miller, Louis H.; Stowers, Anthony W.

doi:10.1086/339187

Cited by 74 publications

(77 citation statements)

References 35 publications

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“…[36][37][38] Several other molecules are being channelled into human trials on the basis of results considered promising and obtained in one of the primate, mouse, or in-vitro models (figure 1). [39][40][41][42][43] Clinical trials will be essential to show whether these results can be extended to human beings.…”

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confidence: 99%

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Guérin¹,

Olliaro

Nosten

et al. 2002

The Lancet Infectious Diseases

320

201

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Section: Personal Viewmentioning

confidence: 99%

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Guérin¹,

Olliaro

Nosten

et al. 2002

The Lancet Infectious Diseases

320

201

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“…Immunization with recombinant forms of MSP3 protected monkeys against malaria infection (8). A vaccine based on MSP3 N-terminal fragment is already in human trials (9,10).…”

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confidence: 99%

Plasmodium falciparum Merozoite Surface Protein 3

Imam

Singh

Kaushik

et al. 2014

Journal of Biological Chemistry

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Background: Plasmodium falciparum merozoite surface protein 3 (MSP3) oligomerizes and binds heme. Results: MSP3 forms amyloid-like structures that bind ϳ35 heme molecules, and these filamentous structures are also present on the surface of merozoites. Conclusion: Amyloid formation by MSP3 is related to heme binding. Significance: The presence of MSP3 fibrils on merozoite surface and significant heme binding suggest its functional role during erythrocytic stages of P. falciparum.

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“…Immunizations with several forms of recombinant MSP3 were each shown to protect monkeys against parasite challenge (4,5). MSP3-specific antibodies in the presence of monocytes mediated killing of parasites in an antibody-dependent cellular inhibition assay (6).…”

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confidence: 99%

Dissection of Merozoite Surface Protein 3, a Representative of a Family of Plasmodium falciparum Surface Proteins, Reveals an Oligomeric and Highly Elongated Molecule

Burgess

Schuck

Garboczi

2005

Journal of Biological Chemistry

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Vaccination with the merozoite surface protein 3 (MSP3) of Plasmodium falciparum protects against infection in primates and is under development as a vaccine against malaria in humans. MSP3 is secreted and associates with the parasite membrane but lacks a predicted transmembrane domain or a glycosylphosphatidylinositol anchor. Its role in the invasion of red blood cells is unclear. To study MSP3, we produced recombinant full-length protein and found by size exclusion chromatography that the apparent size of MSP3 was much larger than predicted from its sequence. To investigate this, we used several biophysical techniques to characterize the fulllength molecule and four smaller polypeptides. The MSP3 polypeptides contain a large amount of ␣-helix and random coil secondary structure as measured by circular dichroism spectroscopy. The fulllength MSP3 forms highly elongated dimers and tetramers as revealed by chemical cross-linking and analytical ultracentrifugation. The dimer is formed through a leucine zipper-like domain located between residues 306 and 362 at the C terminus. Two dimers interact through their C termini to form a tetramer with an apparent association constant of 3 M. Sedimentation velocity experiments determined that the MSP3 molecules are highly extended in solution (some with f/f 0 > 2). These data, in light of the recent discoveries of three other Plasmodium proteins containing very similar C-terminal sequences, suggest that the members of this newly identified family may adopt highly extended and oligomeric novel structures capable of interacting with a red blood cell at relatively long distances.Plasmodium falciparum, the parasitic agent that causes most cases of fatal malaria, is estimated to infect over 500 million people annually (1), causing 1-3 million deaths among young children in sub-Saharan Africa. The rise of parasite resistance to currently available drugs has made malaria treatment difficult. Vaccines have great potential as lower cost alternatives to widespread drug treatment, since they may provide long lived protection from disease. The P. falciparum blood stage surface protein MSP3 2 (2, 3) is a vaccine candidate, since it is known to be a target of the immune response. Immunizations with several forms of recombinant MSP3 were each shown to protect monkeys against parasite challenge (4, 5). MSP3-specific antibodies in the presence of monocytes mediated killing of parasites in an antibody-dependent cellular inhibition assay (6). Homologs to MSP3 have been identified in several Plasmodium species (7-9), indicating that the molecule plays a conserved role in blood stage parasites. The P. falciparum MSP3 sequence predicts several domains ( Fig. 1): a central domain that includes three blocks of imperfect Ala heptad repeats of the sequence pattern Ala-X-X-Ala-X-X-X, a second central region rich in Glu residues, and a C-terminal leucine zipper-like domain (2, 3). Secondary structure algorithms predict MSP3 to be largely ␣-helical, especially in the Ala heptad repeat region that is pre...

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Merozoite Surface Protein 3 and Protection against Malaria inAotus nancymaiMonkeys

Cited by 74 publications

References 35 publications

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Plasmodium falciparum Merozoite Surface Protein 3

Dissection of Merozoite Surface Protein 3, a Representative of a Family of Plasmodium falciparum Surface Proteins, Reveals an Oligomeric and Highly Elongated Molecule

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