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  • 1
    Publication Date: 2002-10-05
    Description: Erythrocyte invasion by Plasmodium falciparum involves multiple ligand-receptor interactions and numerous apparent redundancies. The genome sequence of this parasite reveals new gene families encoding proteins that appear to mediate erythrocyte invasion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowman, Alan F -- Crabb, Brendan S -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):126-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. cowman@wehi.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364790" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Erythrocyte Membrane/parasitology/ultrastructure ; Erythrocytes/metabolism/*parasitology ; Evolution, Molecular ; Genes, Protozoan ; *Genome, Protozoan ; Humans ; Ligands ; Malaria Vaccines ; Merozoite Surface Protein 1/chemistry/metabolism ; Multigene Family ; Plasmodium/pathogenicity/physiology ; Plasmodium falciparum/*genetics/*pathogenicity/physiology/ultrastructure ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/*metabolism ; Receptors, Cell Surface/*metabolism ; Tight Junctions/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-02-05
    Description: Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818761/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818761/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boddey, Justin A -- Hodder, Anthony N -- Gunther, Svenja -- Gilson, Paul R -- Patsiouras, Heather -- Kapp, Eugene A -- Pearce, J Andrew -- de Koning-Ward, Tania F -- Simpson, Richard J -- Crabb, Brendan S -- Cowman, Alan F -- R01 AI044008-11/AI/NIAID NIH HHS/ -- R01 AI44008/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 4;463(7281):627-31. doi: 10.1038/nature08728.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130643" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Antimalarials/pharmacology ; Aspartic Acid Endopeptidases/genetics/isolation & purification/*metabolism ; Endoplasmic Reticulum/enzymology/metabolism ; Erythrocytes/cytology/*metabolism/parasitology ; HIV Protease Inhibitors/pharmacology ; Humans ; Malaria, Falciparum/*blood/metabolism/*parasitology/pathology ; Plasmodium falciparum/enzymology/genetics/*metabolism ; Protein Processing, Post-Translational/drug effects ; *Protein Sorting Signals ; Protein Transport ; Protozoan Proteins/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2008-10-10
    Description: Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656934/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656934/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pain, A -- Bohme, U -- Berry, A E -- Mungall, K -- Finn, R D -- Jackson, A P -- Mourier, T -- Mistry, J -- Pasini, E M -- Aslett, M A -- Balasubrammaniam, S -- Borgwardt, K -- Brooks, K -- Carret, C -- Carver, T J -- Cherevach, I -- Chillingworth, T -- Clark, T G -- Galinski, M R -- Hall, N -- Harper, D -- Harris, D -- Hauser, H -- Ivens, A -- Janssen, C S -- Keane, T -- Larke, N -- Lapp, S -- Marti, M -- Moule, S -- Meyer, I M -- Ormond, D -- Peters, N -- Sanders, M -- Sanders, S -- Sargeant, T J -- Simmonds, M -- Smith, F -- Squares, R -- Thurston, S -- Tivey, A R -- Walker, D -- White, B -- Zuiderwijk, E -- Churcher, C -- Quail, M A -- Cowman, A F -- Turner, C M R -- Rajandream, M A -- Kocken, C H M -- Thomas, A W -- Newbold, C I -- Barrell, B G -- Berriman, M -- 085775/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Oct 9;455(7214):799-803. doi: 10.1038/nature07306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. ap2@sanger.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18843368" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD/chemistry/genetics ; Chromosomes/genetics ; Conserved Sequence ; Genes, Protozoan/genetics ; Genome, Protozoan/*genetics ; *Genomics ; Humans ; Macaca mulatta/*parasitology ; Malaria/*parasitology ; Molecular Sequence Data ; Plasmodium knowlesi/classification/*genetics/physiology ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/genetics ; Sequence Analysis, DNA ; Telomere/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2009-06-19
    Description: Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Koning-Ward, Tania F -- Gilson, Paul R -- Boddey, Justin A -- Rug, Melanie -- Smith, Brian J -- Papenfuss, Anthony T -- Sanders, Paul R -- Lundie, Rachel J -- Maier, Alexander G -- Cowman, Alan F -- Crabb, Brendan S -- R01 AI044008-11/AI/NIAID NIH HHS/ -- R01 AI44008/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter & Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Malaria, Falciparum/*parasitology ; Models, Biological ; Multiprotein Complexes/*chemistry/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-07-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baum, Jake -- Cowman, Alan F -- New York, N.Y. -- Science. 2011 Jul 22;333(6041):410-1. doi: 10.1126/science.1209875.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21778386" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Protozoan/*chemistry/genetics/*metabolism ; Cytoskeleton/metabolism ; *Host-Parasite Interactions ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Plasmodium/chemistry/metabolism/pathogenicity ; Protein Interaction Domains and Motifs ; Protozoan Proteins/*chemistry/genetics/*metabolism ; Toxoplasma/genetics/*metabolism/*pathogenicity/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowman, Alan F -- Tonkin, Christopher J -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):409-10. doi: 10.1126/science.1201692.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia. cowman@wehi.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21273475" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Protozoan/*metabolism ; Cell Division ; Cell Membrane/metabolism ; Membrane Proteins/metabolism ; Phosphorylation ; Protozoan Proteins/*metabolism ; Signal Transduction ; Toxoplasma/cytology/growth & development/*physiology ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2003-02-01
    Description: Transit peptides mediate protein targeting into plastids and are only poorly understood. We extracted amino acid features from transit peptides that target proteins to the relict plastid (apicoplast) of malaria parasites. Based on these amino acid characteristics, we identified 466 putative apicoplast proteins in the Plasmodium falciparum genome. Altering the specific charge characteristics in a model transit peptide by site-directed mutagenesis severely disrupted organellar targeting in vivo. Similarly, putative Hsp70 (DnaK) binding sites present in the transit peptide proved to be important for correct targeting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Foth, Bernardo J -- Ralph, Stuart A -- Tonkin, Christopher J -- Struck, Nicole S -- Fraunholz, Martin -- Roos, David S -- Cowman, Alan F -- McFadden, Geoffrey I -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):705-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, VIC 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12560551" target="_blank"〉PubMed〈/a〉
    Keywords: Acyl Carrier Protein/metabolism ; Algorithms ; Amino Acid Sequence ; Amino Acid Substitution ; Amino Acids/analysis/chemistry ; Animals ; Asparagine/analysis ; Binding Sites ; Computational Biology ; Green Fluorescent Proteins ; HSP70 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Luminescent Proteins/metabolism ; Lysine/analysis ; Models, Biological ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neural Networks (Computer) ; Organelles/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; *Protein Sorting Signals ; *Protein Transport ; Protozoan Proteins/*chemistry/*metabolism ; Vacuoles/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2004-12-14
    Description: To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum. We identified 400 putative erythrocyte-targeted proteins corresponding to approximately 8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marti, Matthias -- Good, Robert T -- Rug, Melanie -- Knuepfer, Ellen -- Cowman, Alan F -- R01-A144008-04A1/PHS HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1930-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591202" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Computational Biology ; Cytoplasm/metabolism ; Erythrocyte Membrane/metabolism ; Gene Expression Profiling ; Genes, Protozoan ; Humans ; Hydrophobic and Hydrophilic Interactions ; Malaria, Falciparum/parasitology ; Membrane Proteins/chemistry/metabolism ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Plasmodium/chemistry/genetics/metabolism ; Plasmodium falciparum/genetics/growth & development/*metabolism/*pathogenicity ; *Protein Sorting Signals ; Protein Transport ; Protozoan Proteins/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Vacuoles/metabolism/parasitology ; Virulence ; Virulence Factors/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2005-08-27
    Description: The malaria parasite, Plasmodium falciparum, exploits multiple ligand-receptor interactions, called invasion pathways, to invade the host erythrocyte. Strains of P. falciparum vary in their dependency on sialated red cell receptors for invasion. We show that switching from sialic acid-dependent to -independent invasion is reversible and depends on parasite ligand use. Expression of P. falciparum reticulocyte-binding like homolog 4 (PfRh4) correlates with sialic acid-independent invasion, and PfRh4 is essential for switching invasion pathways. Differential activation of PfRh4 represents a previously unknown mechanism to switch invasion pathways and provides P. falciparum with exquisite adaptability in the face of erythrocyte receptor polymorphisms and host immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stubbs, Janine -- Simpson, Ken M -- Triglia, Tony -- Plouffe, David -- Tonkin, Christopher J -- Duraisingh, Manoj T -- Maier, Alexander G -- Winzeler, Elizabeth A -- Cowman, Alan F -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2005 Aug 26;309(5739):1384-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16123303" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Erythrocytes/*parasitology ; Gene Expression Profiling ; Gene Silencing ; Genes, Protozoan ; Humans ; Ligands ; Membrane Proteins/analysis/genetics/*physiology ; Neuraminidase/pharmacology ; Oligonucleotide Array Sequence Analysis ; Plasmodium falciparum/genetics/growth & development/metabolism/*pathogenicity ; Polymerase Chain Reaction ; Protozoan Proteins/analysis/genetics/*physiology ; Recombinant Fusion Proteins/metabolism ; Sialic Acids/metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2006-09-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowman, Alan F -- Kappe, Stefan H I -- New York, N.Y. -- Science. 2006 Sep 1;313(5791):1245-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia. cowman@wehi.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946056" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cell Adhesion ; Cell Death ; Cell Membrane/metabolism ; Cells, Cultured ; Cellular Structures/*parasitology/ultrastructure ; Endothelial Cells/parasitology ; Erythrocytes/parasitology ; Hepatocytes/*parasitology/physiology/ultrastructure ; Liver/blood supply/parasitology ; Malaria/*parasitology ; Mice ; Phagocytosis ; Phosphatidylserines/metabolism ; Plasmodium berghei/growth & development/*pathogenicity ; Sporozoites/growth & development ; Vacuoles/parasitology/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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