Structural studies on Plasmodium vivax merozoite surface protein-1.
Plasmodium vivax infection is the second most common cause of malaria throughout the world. Like other Plasmodium species, P. vivax has a large protein complex, MSP-1, located on the merozoite surface. The C-terminal MSP-1 sub-unit, MSP-1(42), is cleaved during red blood cell invasion, causing the majority of the complex to be shed and leaving only a small 15kDa sub-unit, MSP-1(19), on the merozite surface. MSP-1(19) is considered a strong vaccine candidate. We have determined the solution structure of MSP-1(19) from P. vivax using nuclear magnetic resonance (NMR) and show that, like in other Plasmodium species, it consists of two EGF-like domains that are oriented head-to-tail. The protein has a flat, disk-like shape with a highly charged surface. When MSP-1(19) is part of the larger MSP-1(42) precursor it exists as an independent domain with no stable contacts to the rest of the sub-unit. Gel filtration and analytical ultracentrifugation experiments indicate that P. vivax MSP-1(42) exists as a dimer in solution. MSP-1(19) itself is a monomer, however, 35 amino-acids immediately upstream of its N-terminus are sufficient to cause dimerization. Our data suggest that if MSP-1(42) exists as a dimer in vivo, secondary processing would cause the dissociation of two tightly linked MSP-1(19) proteins on the merozoite surface just prior to invasion.
Babon
Jeffrey J
JJ
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. babon@wehi.EDU.AU
Morgan
William D
WD
Kelly
Geoffrey
G
Eccleston
John F
JF
Feeney
James
J
Holder
Anthony A
AA
D000818:Animals; D019281:Dimerization; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D046912:Multiprotein Complexes; D019906:Nuclear Magnetic Resonance, Biomolecular; D010966:Plasmodium vivax / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity
D020066:Merozoite Surface Protein 1; D046912:Multiprotein Complexes; D021122:Protein Subunits; D011994:Recombinant Proteins