title: Analysis of the conformation and function of the Plasmodium falciparum merozoite proteins MTRAP and PTRAMP.
abstract: Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium falciparum proteins containing TSR domains play crucial roles in parasite development. In particular, the preerythrocytic P. falciparum circumsporozoite protein is involved in hepatocyte invasion. The importance of these domains in two other malaria proteins, the merozoite-specific thrombospondin-related anonymous protein (MTRAP) and the thrombospondin-related apical membrane protein (PTRAMP), were assessed using near-full-length recombinant proteins composed of the extracellular domains produced in Escherichia coli. MTRAP is thought to be released from invasive organelles identified as micronemes during merozoite invasion to mediate motility and host cell invasion through an interaction with aldolase, an actin binding protein involved in the moving junction. PTRAMP function remains unknown. In this study, the conformation of recombinant MTRAP (rMTRAP) appeared to be a highly extended protein (2 nm by 33 nm, width by length, respectively), whereas rPTRAMP had a less extended structure. Using an erythrocyte binding assay, rMTRAP but not rPTRAMP bound human erythrocytes; rMTRAP binding was mediated through the TSR domain. MTRAP- and in general PTRAMP-specific antibodies failed to inhibit P. falciparum development in vitro. Altogether, MTRAP is a highly extended bifunctional protein that binds to an erythrocyte receptor and the merozoite motor.
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Onyinyechukwu
authors.initials: O
authors.lastname: Uchime
authors.forename: Raul
authors.initials: R
authors.lastname: Herrera
authors.forename: Karine
authors.initials: K
authors.lastname: Reiter
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kotova
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shimp
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Dominique
authors.initials: D
authors.lastname: Jones
authors.forename: Jacob
authors.initials: J
authors.lastname: Lebowitz
authors.forename: Xavier
authors.initials: X
authors.lastname: Ambroggio
authors.forename: Darrell E
authors.initials: DE
authors.lastname: Hurt
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Jin
authors.forename: Carole
authors.initials: C
authors.lastname: Long
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D055592:Biophysical Phenomena; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019295:Computational Biology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D004926:Escherichia coli / Q000737:chemistry; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry; D017125:Genes, Protozoan; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000254:growth & development / Q000276:immunology; D011485:Protein Binding; D058849:Protein Refolding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D063267:Sialic Acid Binding Ig-like Lectin 1; D014461:Ultracentrifugation; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C487867:PTRAMP protein, Plasmodium; D015800:Protozoan Proteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D005634:Fructose-Bisphosphate Aldolase