Open AccessAnalysis of the Conformation and Function of the Plasmodium falciparum Merozoite Proteins MTRAP and PTRAMP
Author(s) -
Onyinyechukwu Uchime,
Raúl Herrera,
Karine Reiter,
Svetlana Kotova,
Richard L. Shimp,
Kazutoyo Miura,
Dominique Jones,
Jacob Lebowitz,
Xavier Ambroggio,
Darrell E. Hurt,
Albert J. Jin,
Carole A. Long,
Louis H. Miller,
David L. Narum
Publication year - 2012
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.00039-12
Subject(s) - biology , plasmodium falciparum , microneme , thrombospondin , circumsporozoite protein , microbiology and biotechnology , transmembrane protein , gliding motility , binding protein , recombinant dna , motility , receptor , biochemistry , apicomplexa , metalloproteinase , gene , malaria , matrix metalloproteinase , immunology
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.