title: A repeat sequence domain of the ring-exported protein-1 of Plasmodium falciparum controls export machinery architecture and virulence protein trafficking.
abstract: The malaria parasite Plasmodium falciparum dramatically remodels its host red blood cell to enhance its own survival, using a secretory membrane system that it establishes outside its own cell. Cisternal organelles, called Maurer's clefts, act as a staging point for the forward trafficking of virulence proteins to the red blood cell (RBC) membrane. The Ring-EXported Protein-1 (REX1) is a Maurer's cleft resident protein. We show that inducible knockdown of REX1 causes stacking of Maurer's cleft cisternae without disrupting the organization of the knob-associated histidine-rich protein at the RBC membrane. Genetic dissection of the REX1 sequence shows that loss of a repeat sequence domain results in the formation of giant Maurer's cleft stacks. The stacked Maurer's clefts are decorated with tether-like structures and retain the ability to dock onto the RBC membrane skeleton. The REX1 mutant parasites show deficient export of the major virulence protein, PfEMP1, to the red blood cell surface and markedly reduced binding to the endothelial cell receptor, CD36. REX1 is predicted to form a largely α-helical structure, with a repetitive charge pattern in the repeat sequence domain, providing potential insights into the role of REX1 in Maurer's cleft sculpting.
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Emma
authors: E
authors: McHugh
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Steven
authors: S
authors: Batinovic
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.|Advanced Microscopy Facility, University of Melbourne, Parkville, VIC, 3010, Australia.
authors: Eric
authors: E
authors: Hanssen
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.|Biological Optical Microscopy Platform, Bio21 Molecular Science and Biotechnology Institute, Parkville, VIC, 3010, Australia.
authors: Paul J
authors: PJ
authors: McMillan
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Shannon
authors: S
authors: Kenny
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Michael D W
authors: MD
authors: Griffin
authors: School of BioSciences, University of Melbourne, Parkville, VIC, 3010, Australia.
authors: Simon
authors: S
authors: Crawford
authors: Infectious Diseases Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD, 4006, Australia.
authors: Katharine R
authors: KR
authors: Trenholme
authors: Infectious Diseases Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD, 4006, Australia.
authors: Donald L
authors: DL
authors: Gardiner
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Matthew W A
authors: MW
authors: Dixon
authors: Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors: Leann
authors: L
authors: Tilley
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism; D016054:DNA, Protozoan; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D055785:Gene Knockdown Techniques; D006801:Humans; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000099053:Histidine-Rich Glycoprotein
chemical_list: D018955:CD36 Antigens; D016054:DNA, Protozoan; D011506:Proteins; D015800:Protozoan Proteins; C541886:REX1 protein, Plasmodium falciparum; D037521:Virulence Factors; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D000099053:Histidine-Rich Glycoprotein