title: A Schistosoma japonicum very low-density lipoprotein-binding protein.
abstract: Schistosomes acquire fatty acids from their hosts, although how these parasites bind human low-density lipoproteins (LDL) and like molecules that transport fatty acids is not understood. Because parasite surface-bound host LDL may provide the schistosome with cholesterol and other lipids, as well as aid immune avoidance, understanding this process may provide fundamental insights into lipid metabolism and host defense in schistosomes. To investigate molecular aspects of lipid acquisition by schistosomes, transcripts encoding a very (V)LDL-receptor ligand binding, cysteine-rich repeat-containing protein were isolated from Schistosoma japonicum cDNAs. The deduced amino acid sequence included 207 residues with an NH2-terminal LDL ligand-binding Cys-rich motif and a COOH-terminal transmembrane (TM) domain. The ligand-binding domain was similar in sequence and structure to ligand-binding Cys-rich repeat domains from mammalian very low-density lipoprotein (VLDL) and LDL receptors, which are multi-domain proteins. This putative VLDL binding protein, designated S. japonicum very low-density lipoprotein binding protein (SVLBP), appeared to be membrane-associated, sensitive to reducing conditions, and included intra-molecular disulfide linkages. A three-dimensional (3D) model suggested that two of the three Cys residues form intra- and/or inter-molecular disulfide bridges that contribute to a patch of negative charge on the molecular surface, assumed to be associated with VLDL binding activity. SVLBP in membrane-associated and soluble fractions of adult schistosomes bound human plasma VLDL in vitro, and VLDL bound to recombinant SVLBP inhibited the binding of anti-recombinant SVLBP antibodies. Immunolocalization of SVLBP revealed prominent expression in the tegument and sub-tegument of adult male schistosomes. SVLBP may play a key role in lipid acquisition by S. japonicum.
authors.affiliation: Molecular Parasitology Unit, Queensland Institute of Medical Research, Brisbane, Qld, Australia.
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Fan
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Gan
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.forename: Liying
authors.initials: L
authors.lastname: Shen
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015139:Blotting, Southern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D003553:Cystine / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004765:Enteropeptidase / Q000235:genetics / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012549:Schistosoma japonicum / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D011994:Recombinant Proteins; C036053:VLDL receptor; D003553:Cystine; D004765:Enteropeptidase