semaphorin-7a is an erythrocyte receptor for p. falciparum merozoite-specific trap homolog, mtrapsemaphorin-7a是恶性疟原虫的红细胞受体merozoite-specific陷阱同族体,mtrap.pdfVIP

Semaphorin-7A Is an Erythrocyte Receptor for P. falciparum Merozoite-Specific TRAP Homolog, MTRAP 1,2 2 1,2 3 3 S. Josefin Bartholdson , Leyla Y. Bustamante , Cecile Crosnier , Steven Johnson , Susan Lea , Julian C. Rayner2, Gavin J. Wright1,2* 1 Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, 2 Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, 3 Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom Abstract The motility and invasion of Plasmodium parasites is believed to require a cytoplasmic actin-myosin motor associated with a cell surface ligand belonging to the TRAP (thrombospondin-related anonymous protein) family. Current models of invasion usually invoke the existence of specific receptors for the TRAP-family ligands on the surface of the host cell; however, the identities of these receptors remain largely unknown. Here, we identify the GPI-linked protein Semaphorin-7A (CD108) as an erythrocyte receptor for the P. falciparum merozoite-specific TRAP homolog (MTRAP) by using a systematic screening approach designed to detect extracellular protein interactions. The specificity of the interaction was demonstrated by showing that binding was saturable and by quantifying the equilibrium and kinetic biophysical binding parameters using surface plasmon resonance. We found that two MTRAP monomers interact via their tandem TSR domains with the Sema domains of a Semaphorin-7A homodimer. Known naturally-occurring polymorphisms in Semaphorin-7A did not quantitatively affect MTRAP binding nor did