title: The merozoite surface protein 1 complex is a platform for binding to human erythrocytes by Plasmodium falciparum.
abstract: Plasmodium falciparum is the causative agent of the most severe form of malaria in humans. The merozoite, an extracellular stage of the parasite lifecycle, invades erythrocytes in which they develop. The most abundant protein on the surface of merozoites is merozoite surface protein 1 (MSP1), which consists of four processed fragments. Studies indicate that MSP1 interacts with other peripheral merozoite surface proteins to form a large complex. Successful invasion of merozoites into host erythrocytes is dependent on this protein complex; however, the identity of all components and its function remain largely unknown. We have shown that the peripheral merozoite surface proteins MSPDBL1 and MSPDBL2 are part of the large MSP1 complex. Using surface plasmon resonance, we determined the binding affinities of MSPDBL1 and MSPDBL2 to MSP1 to be in the range of 2-4 × 10(-7) m. Both proteins bound to three of the four proteolytically cleaved fragments of MSP1 (p42, p38, and p83). In addition, MSPDBL1 and MSPDBL2, but not MSP1, bound directly to human erythrocytes. This demonstrates that the MSP1 complex acts as a platform for display of MSPDBL1 and MSPDBL2 on the merozoite surface for binding to receptors on the erythrocyte and invasion.
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia, Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia.
authors: Clara S
authors: CS
authors: Lin
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.
authors: Alessandro D
authors: AD
authors: Uboldi
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia, Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia.
authors: Danushka
authors: D
authors: Marapana
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia, Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia.
authors: Peter E
authors: PE
authors: Czabotar
authors: Department of Infectious Diseases, Parasitology, Universität Heidelberg, INF 324, D-69120 Heidelberg, Germany.
authors: Christian
authors: C
authors: Epp
authors: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), INF 282, D-69120 Heidelberg, Germany, and.
authors: Hermann
authors: H
authors: Bujard
authors: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3082, Australia.
authors: Nicole L
authors: NL
authors: Taylor
authors: Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3082, Australia.
authors: Matthew A
authors: MA
authors: Perugini
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia, Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia, hodder@wehi.edu.au.
authors: Anthony N
authors: AN
authors: Hodder
authors: From the The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia, Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia, cowman@wehi.edu.au.
authors: Alan F
authors: AF
authors: Cowman
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000378:metabolism*; D052940:Merozoites / Q000737:chemistry*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D046912:Multiprotein Complexes; D015800:Protozoan Proteins
keywords: Cell Invasion; Complex; Infection; Malaria; Merozoite; Parasite; Plasmodium; Protein Complex; falciparum