Structural studies on Plasmodium vivax merozoite surface protein-1

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• 作者：Jeffrey J. Babon ; William D. Morgan ; Geoffrey Kelly ; John F. Eccleston ; James Feeney ; Anthony A. Holder
• 关键词：Malaria ; Plasmodium vivax ; MSP-1 structure ; Dimer ; Merozoite surface protein
• 刊名：Molecular and Biochemical Parasitology
• 出版年：2007
• 期刊代码：108_01666851
• 类别：bio
• 出版时间：May 2007
• 卷：153
• 期：1
• 页码：31-40
• 文件大小：1037 K

摘要

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.