Structure of Plasmodium falciparum TRAP (thrombospondin-related anonymous protein) A domain highlights distinct features in apicomplexan von Willebrand factor A homologues.

Abstract	TRAP (thrombospondin-related anonymous protein), localized in the micronemes and on the surface of sporozoites of the notorious malaria parasite Plasmodium, is a key molecule upon infection of mammalian host hepatocytes and invasion of mosquito salivary glands. TRAP contains two adhesive domains responsible for host cell recognition and invasion, and is known to be essential for infectivity. In the present paper, we report high-resolution crystal structures of the A domain of Plasmodium falciparum TRAP with and without bound Mg2+. The structure reveals a vWA (von Willebrand factor A)-like fold and a functional MIDAS (metal-ion-dependent adhesion site), as well as a potential heparan sulfate-binding site. Site-directed mutagenesis and cell-attachment assays were used to investigate the functional roles of the surface epitopes discovered. The reported structures are the first determined for a complete vWA domain of parasitic origin, highlighting unique features among homologous domains from other proteins characterized hitherto. Some of these are conserved among Plasmodiae exclusively, whereas others may be common to apicomplexan organisms in general.
Authors	Tero Pihlajamaa, Tommi Kajander, Juho Knuuti, Kaisa Horkka, Amit Sharma, Perttu Permi
Journal	The Biochemical journal (Biochem J) Vol. 450 Issue 3 Pg. 469-76 (Mar 15 2013) ISSN: 1470-8728 [Electronic] England
PMID	23317521 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Protozoan Proteins Recombinant Proteins von Willebrand Factor thrombospondin-related adhesive protein, protozoan
Topics	Animals Apicomplexa (genetics, metabolism) Crystallography, X-Ray Models, Molecular Mutagenesis, Site-Directed Plasmodium falciparum (chemistry, genetics) Protein Folding Protein Interaction Domains and Motifs (genetics, physiology) Protozoan Proteins (chemistry, genetics, metabolism) Recombinant Proteins (chemistry, isolation & purification, metabolism) Sequence Homology von Willebrand Factor (chemistry, genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!