title: Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes.
abstract: Successful invasion of human erythrocytes byPlasmodium falciparummerozoites is required for infection of the host and parasite survival. The early stages of invasion are mediated via merozoite surface proteins that interact with human erythrocytes. The nature of these interactions are currently not well understood, but it is known that merozoite surface protein 1 (MSP1) is critical for successful erythrocyte invasion. Here we show that the peripheral merozoite surface proteins MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 bind directly to MSP1, but independently of each other, to form multiple forms of the MSP1 complex on the parasite surface. These complexes have overlapping functions that interact directly with human erythrocytes. We also show that targeting the p83 fragment of MSP1 using inhibitory antibodies inhibits all forms of MSP1 complexes and disrupts parasite growthin vitro.
authors.affiliation: From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, the Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Clara S
authors.initials: CS
authors.lastname: Lin
authors.affiliation: From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Uboldi
authors.affiliation: the Department of Infectious Diseases, Parasitology, Universität Heidelberg, INF 324, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Epp
authors.affiliation: the Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany, and.
authors.forename: Hermann
authors.initials: H
authors.lastname: Bujard
authors.affiliation: the Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, the Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Czabotar
authors.affiliation: From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, the Department of Medical Biology, University of Melbourne, Melbourne, Australia, cowman@wehi.edu.au.
authors.forename: Alan F
authors.identifier: http://orcid.org/0000-0001-5145-9004
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000378:metabolism*; D052940:Merozoites / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*
chemical_list: D020066:Merozoite Surface Protein 1; D046912:Multiprotein Complexes
keywords: erythrocyte; infectious disease; invasion; malaria; protein complex
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7509-14
references.pmid: 10861015
references.citation: Mol Biochem Parasitol. 2001 Jan 15;112(1):91-101
references.pmid: 11166390
references.citation: J Exp Med. 2001 Jun 18;193(12):1403-12
references.pmid: 11413195
references.citation: Mol Microbiol. 2001 Jul;41(1):47-58
references.pmid: 11454199
references.citation: J Biol Chem. 2001 Aug 17;276(33):31311-20
references.pmid: 11399764
references.citation: Mol Biochem Parasitol. 2001 Sep 28;117(1):83-9
references.pmid: 11551634
references.citation: Mol Microbiol. 2002 Mar;43(6):1401-11
references.pmid: 11952894
references.citation: EMBO J. 2003 Mar 3;22(5):1047-57
references.pmid: 12606570
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5164-9
references.pmid: 12692305
references.citation: J Biol Chem. 2003 Jul 25;278(30):27354-61
references.pmid: 12748176
references.citation: J Biol Chem. 2004 Feb 13;279(7):5765-71
references.pmid: 14630931
references.citation: Cell Microbiol. 2004 Oct;6(10):893-903
references.pmid: 15339265
references.citation: Mol Biochem Parasitol. 1987 Feb;23(1):71-84
references.pmid: 2437453
references.citation: Parasitology. 1987 Apr;94 ( Pt 2):199-208
references.pmid: 3295686
references.citation: Exp Parasitol. 1990 Feb;70(2):193-206
references.pmid: 2404781
references.citation: J Exp Med. 1990 Jul 1;172(1):379-82
references.pmid: 1694225
references.citation: J Exp Med. 1990 Dec 1;172(6):1633-41
references.pmid: 2258697
references.citation: Mol Biochem Parasitol. 1991 Nov;49(1):29-33
references.pmid: 1775158
references.citation: Mol Biochem Parasitol. 1991 Nov;49(1):35-44
references.pmid: 1723148
references.citation: Mol Biochem Parasitol. 1992 Feb;50(2):307-15
references.pmid: 1741018
references.citation: Mol Biochem Parasitol. 1993 Nov;62(1):103-14
references.pmid: 8114810
references.citation: Exp Parasitol. 1994 May;78(3):259-68
references.pmid: 7512929
references.citation: Blood. 1994 Sep 1;84(5):1594-602
references.pmid: 8068948
references.citation: Mol Biochem Parasitol. 1994 Jul;66(1):157-60
references.pmid: 7984180
references.citation: Mol Biochem Parasitol. 1994 Sep;67(1):59-68
references.pmid: 7838184
references.citation: Mol Biochem Parasitol. 1996 Oct 1;80(2):159-69
references.pmid: 8892293
references.citation: Infect Immun. 2005 Feb;73(2):1235-8
references.pmid: 15664972
references.citation: Protein Sci. 2005 Jul;14(7):1778-86
references.pmid: 15987906
references.citation: Science. 2005 Aug 26;309(5739):1384-7
references.pmid: 16123303
references.citation: Infect Immun. 2005 Oct;73(10):6981-9
references.pmid: 16177378
references.citation: J Biol Chem. 2005 Nov 4;280(44):37236-45
references.pmid: 16135515
references.citation: PLoS Med. 2005 Nov;2(11):e344
references.pmid: 16262450
references.citation: Infect Immun. 2006 Feb;74(2):1313-22
references.pmid: 16428781
references.citation: Cell. 2006 Feb 24;124(4):755-66
references.pmid: 16497586
references.citation: Mol Cell Proteomics. 2006 Jul;5(7):1286-99
references.pmid: 16603573
references.citation: J Biol Chem. 2006 Oct 20;281(42):31517-27
references.pmid: 16940297
references.citation: Mol Biochem Parasitol. 2007 Jan;151(1):59-69
references.pmid: 17097159
references.citation: Mol Biochem Parasitol. 2007 Aug;154(2):148-57
references.pmid: 17553576
references.citation: Int J Parasitol. 2009 Jun;39(7):763-73
references.pmid: 19367830
references.citation: PLoS One. 2009;4(4):e5410
references.pmid: 19404387
references.citation: Mol Biochem Parasitol. 2009 Jun;165(2):153-61
references.pmid: 19428662
references.citation: PLoS One. 2009;4(5):e5568
references.pmid: 19440377
references.citation: Eukaryot Cell. 2010 Jul;9(7):1064-74
references.pmid: 20472690
references.citation: Trends Parasitol. 2010 Jul;26(7):363-9
references.pmid: 20466591
references.citation: Mol Biol Evol. 2010 Oct;27(10):2344-51
references.pmid: 20457586
references.citation: PLoS Genet. 2011 Apr;7(4):e1001383
references.pmid: 21533027
references.citation: Infect Immun. 2012 Mar;80(3):1280-7
references.pmid: 22202121
references.citation: Vaccine. 2012 Mar 2;30(11):1972-80
references.pmid: 22248820
references.citation: J Biol Chem. 2012 Sep 21;287(39):32922-39
references.pmid: 22843685
references.citation: PLoS Genet. 2012;8(11):e1002992
references.pmid: 23133397
references.citation: J Biol Chem. 2014 Feb 14;289(7):3856-68
references.pmid: 24362023
references.citation: Sci Transl Med. 2014 Jul 30;6(247):247ra102
references.pmid: 25080477
references.citation: J Biol Chem. 2014 Sep 12;289(37):25655-69
references.pmid: 25074930
references.citation: Blood. 2015 Apr 23;125(17):2704-11
references.pmid: 25778531
references.citation: J Infect Dis. 2015 Aug 1;212(3):406-15
references.pmid: 25646353
references.citation: Cell Host Microbe. 2015 Oct 14;18(4):433-44
references.pmid: 26468747