The malaria vaccine development program in Papua New Guinea

Genton, Blaise; Anders, Robin F.; Alpers, Michael P.; Reeder, John C.

doi:10.1016/s1471-4922(03)00111-9

Cited by 17 publications

(8 citation statements)

References 36 publications

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“…Merozoite surface protein 2 (MSP2) is one of the most abundant proteins on the merozoite surface of Plasmodium falciparum, which proved to be a promising anti-malaria vaccine target [377,378]. MSP2 is a glycosyl-phosphatidylinositol anchored protein of mass approximately 30 kDa [379].…”

Section: Merozoite Surface Protein 2 (Msp2)mentioning

confidence: 99%

Amyloidogenesis of Natively Unfolded Proteins

Uversky

2008

CAR

172

152

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Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.

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Section: Merozoite Surface Protein 2 (Msp2)mentioning

confidence: 99%

Amyloidogenesis of Natively Unfolded Proteins

Uversky

2008

CAR

172

152

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“…1 We and others have conducted a number of epidemiologic surveys within PNG to improve our understanding of the relationships between malaria parasite infection and disease, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] anti-malarial drug and vaccine effectiveness, [17][18][19] and human genetic polymorphisms. [20][21][22][23][24][25][26][27][28] These studies have shown that all four Plasmodium species (P. falciparum [PF], P. vivax [PV], P. malariae [PM], and P. ovale [PO]) cause infection in PNG.…”

Section: Introductionmentioning

confidence: 99%

Changing Patterns of Plasmodium Blood-Stage Infections in the Wosera Region of Papua New Guinea Monitored by Light Microscopy and High Throughput PCR Diagnosis

Kasehagen

Müeller

McNamara

et al. 2006

The American Journal of Tropical Medicine and Hygiene

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104

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“…MSP2 proved to be a promising vaccine target in a field study conducted in Papua New Guinea. [3][4][5] In addition, vaccine trials have shown that an 8-residue peptide from the N-terminal region of MSP2 (MSP2 [8][9][10][11][12][13][14][15] ) provides some level of immunity against rodent malarial parasites. 6,7 MSP2 is a glycosyl-phosphatidyl-inositol (GPI) anchored protein of mass $30 kDa.…”

Section: Introductionmentioning

confidence: 99%

Merozoite surface protein 2 of Plasmodium falciparum: Expression, structure, dynamics, and fibril formation of the conserved N‐terminal domain

et al. 2007

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Merozoite surface protein 2 (MSP2) is a GPI-anchored protein on the surface of the merozoite stage of the malaria parasite Plasmodium falciparum. It is largely disordered in solution, but has a propensity to form amyloid-like fibrils under physiological conditions. The N-terminal conserved region (MSP2(1-25)) is part of the protease-resistant core of these fibrils. To investigate the structure and dynamics of this region, its ability to form fibrils, and the role of individual residues in these properties, we have developed a bacterial expression system that yields > or =10 mg of unlabeled or (15)N-labeled peptide per litre of culture. Two recombinant versions of MSP2(1-25), wild-type and a Y7A/Y16A mutant, have been produced. Detailed conformational analysis of the wild-type peptide and backbone (15)N relaxation data indicated that it contains beta-turn and nascent helical structures in the central and C-terminal regions. Residues 6-21 represent the most ordered region of the structure, although there is some flexibility around residues 8 and 9. The 10-residue sequence (MSP2(7-16)) (with two Tyr residues) was predicted to have a higher propensity for beta-aggregation than the 8-mer sequence (MSP2(8-15)), but there was no significant difference in conformation between MSP2(1-25) and [Y7A,Y16A]MSP2(1-25) and the rate of fibril formation was only slightly slower in the mutant. The peptide expression system described here will facilitate further mutational analyses to define the roles of individual residues in transient structural elements and fibril formation, and thus contribute to the further development of MSP2 as a malaria vaccine candidate.

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The malaria vaccine development program in Papua New Guinea

Cited by 17 publications

References 36 publications

Amyloidogenesis of Natively Unfolded Proteins

Amyloidogenesis of Natively Unfolded Proteins

Changing Patterns of Plasmodium Blood-Stage Infections in the Wosera Region of Papua New Guinea Monitored by Light Microscopy and High Throughput PCR Diagnosis

Merozoite surface protein 2 of Plasmodium falciparum: Expression, structure, dynamics, and fibril formation of the conserved N‐terminal domain

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