title: Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells.
abstract: During development inside red blood cells (RBCs), Plasmodium falciparum malaria parasites export proteins that associate with the RBC membrane skeleton. These interactions cause profound changes to the biophysical properties of RBCs that underpin the often severe and fatal clinical manifestations of falciparum malaria. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is one such exported parasite protein that plays a major role in malaria pathogenesis since its exposure on the parasitised RBC surface mediates their adhesion to vascular endothelium and placental syncytioblasts. En route to the RBC membrane skeleton, PfEMP1 transiently associates with Maurer's clefts (MCs), parasite-derived membranous structures in the RBC cytoplasm. We have previously shown that a resident MC protein, skeleton-binding protein 1 (SBP1), is essential for the placement of PfEMP1 onto the RBC surface and hypothesised that the function of SBP1 may be to target MCs to the RBC membrane. Since this would require additional protein interactions, we set out to identify binding partners for SBP1. Using a combination of approaches, we have defined the region of SBP1 that binds specifically to defined sub-domains of two major components of the RBC membrane skeleton, protein 4.1R and spectrin. We show that these interactions serve as one mechanism to anchor MCs to the RBC membrane skeleton, however, while they appear to be necessary, they are not sufficient for the translocation of PfEMP1 onto the RBC surface. The N-terminal domain of SBP1 that resides within the lumen of MCs clearly plays an essential, but presently unknown role in this process.
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Lev M
authors.initials: LM
authors.lastname: Kats
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Proellocks
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Donna W
authors.initials: DW
authors.lastname: Buckingham
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: Lionel
authors.initials: L
authors.lastname: Blanc
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hale
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Guo
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Susann
authors.initials: S
authors.lastname: Herrmann
authors.affiliation: Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Hanssen
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.affiliation: New York Blood Center, New York, NY 10021, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
authors.affiliation: Department of Microbiology, Monash University, Victoria 3800, Australia.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cooke
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D006790:Host-Parasite Interactions; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C028841:erythrocyte membrane band 4.1 protein; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D013049:Spectrin
keywords: Cell adhesion and mechanics; Malaria; Plasmodium falciparum; Protein 4.1R; Red blood cell; Spectrin