title: The layered fold of the TSR domain of P. falciparum TRAP contains a heparin binding site.
abstract: Thrombospondin-related anonymous protein, TRAP, has a critical role in the hepatocyte invasion step of Plasmodium sporozoites, the transmissible form of the parasite causing malaria. The extracellular domains of this sporozoite surface protein interact with hepatocyte surface receptors whereas its intracellular domain acts as a link to the sporozoite actomyosin motor system. Liver heparan sulfate proteoglycans have been identified as potential ligands for TRAP. Proteoglycan binding has been associated with the A- and TSR domains of TRAP. We present the solution NMR structure of the TSR domain of TRAP and a chemical shift mapping study of its heparin binding epitope. The domain has an elongated structure stabilized by an array of tryptophan and arginine residues as well as disulfide bonds. The fold is very similar to those of thrombospondin type-1 (TSP-1) and F-spondin TSRs. The heparin binding site of TRAP-TSR is located in the N-terminal half of the structure, the layered side chains forming an integral part of the site. The smallest heparin fragment capable of binding to TRAP-TSR is a tetrasaccharide.
authors.affiliation: Program in Structural Biology and Biophysics, NMR Laboratory, Institute of Biotechnology, Neuroscience Center, Department of Chemistry, University of Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Tossavainen
authors.forename: Tero
authors.initials: T
authors.lastname: Pihlajamaa
authors.forename: Toni K
authors.initials: TK
authors.lastname: Huttunen
authors.forename: Erkki
authors.initials: E
authors.lastname: Raulo
authors.forename: Heikki
authors.initials: H
authors.lastname: Rauvala
authors.forename: Perttu
authors.initials: P
authors.lastname: Permi
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kilpeläinen
mesh_terms: D000818:Animals; D001665:Binding Sites; D006493:Heparin / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000472:pathogenicity; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan; D006493:Heparin