TY - JOUR
T1 - Structural studies on Plasmodium vivax merozoite surface protein-1
AU - Babon, Jeffrey J.
AU - Morgan, William D.
AU - Kelly, Geoffrey
AU - Eccleston, John F.
AU - Feeney, James
AU - Holder, Anthony A.
N1 - Funding Information:
This study was funded by the Medical Research Council, UK and by the European Commission through the EUROMALVAC Consortium, contracts QLK2-CT-1999-01293 and QLK2-CT-2002-01197.
PY - 2007/5
Y1 - 2007/5
N2 - 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-142, is cleaved during red blood cell invasion, causing the majority of the complex to be shed and leaving only a small 15 kDa sub-unit, MSP-119, on the merozite surface. MSP-119 is considered a strong vaccine candidate. We have determined the solution structure of MSP-119 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-119 is part of the larger MSP-142 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-142 exists as a dimer in solution. MSP-119 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-142 exists as a dimer in vivo, secondary processing would cause the dissociation of two tightly linked MSP-119 proteins on the merozoite surface just prior to invasion. Crown
AB - 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-142, is cleaved during red blood cell invasion, causing the majority of the complex to be shed and leaving only a small 15 kDa sub-unit, MSP-119, on the merozite surface. MSP-119 is considered a strong vaccine candidate. We have determined the solution structure of MSP-119 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-119 is part of the larger MSP-142 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-142 exists as a dimer in solution. MSP-119 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-142 exists as a dimer in vivo, secondary processing would cause the dissociation of two tightly linked MSP-119 proteins on the merozoite surface just prior to invasion. Crown
KW - Dimer
KW - MSP-1 structure
KW - Malaria
KW - Merozoite surface protein
KW - Plasmodium vivax
UR - http://www.scopus.com/inward/record.url?scp=34047189721&partnerID=8YFLogxK
U2 - 10.1016/j.molbiopara.2007.01.015
DO - 10.1016/j.molbiopara.2007.01.015
M3 - Article
C2 - 17343930
AN - SCOPUS:34047189721
SN - 0166-6851
VL - 153
SP - 31
EP - 40
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 1
ER -