Structural studies on Plasmodium vivax merozoite surface protein-1
- Author(s)
- Babon, JJ; Morgan, WD; Kelly, G; Eccleston, JF; Feeney, J; Holder, AA;
- Details
- Publication Year 2007-05,Volume 153,Issue #1,Page 31-40
- Journal Title
- MOLECULAR AND BIOCHEMICAL PARASITOLOGY
- Publication Type
- Journal Article
- Abstract
- 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 15 kDa 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. Crown Copyright (C) 2007 Published by Elsevier B.V. All rights reserved.
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- MALARIA VACCINE CANDIDATE; C-TERMINAL FRAGMENT; ERYTHROCYTE INVASION; MONOCLONAL-ANTIBODY; FALCIPARUM MEROZOITES; INHIBITORY ANTIBODIES; CRYSTAL-STRUCTURE; FINE SPECIFICITY; TROSY NMR; IN-VITRO
- Publisher's Version
- https://doi.org/10.1016/j.molbiopara.2007.01.015
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-05-01 12:00:00