The International Journal of Biochemistry & Cell Biology 35 (2003) 1436–1451 A Schistosoma japonicum very low-density lipoprotein-binding protein  Jinjiang Fan a,b,c,d , Xiaoxian Gan c , Wen Yang a,b,e , Liying Shen c , Donald P. McManus a,b , Paul J. Brindley a,b,f,∗ a Molecular Parasitology Unit, Queensland Institute of Medical Research, Brisbane, Qld, Australia b Australian Centre for International & Tropical Health & Nutrition, The University of Queensland, Brisbane, Qld 4029, Australia c Institute of Parasitic Diseases, Zhejiang Academy of Medical Sciences, Hangzhou 310013, Zhejiang, PR China d Mammalian Cell Genetics Group, Health Sector, N.R.C. Biotechnology Research Institute, Montreal, Que., Canada H4P 2R2 e Immunochemistry Laboratory, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA f Department of Tropical Medicine, School of Public Health & Tropical Medicine, Center for Infectious Diseases, Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112, USA Received 8 December 2002; received in revised form 25 February 2003; accepted 25 February 2003 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 NH 2 -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. © 2003 Elsevier Science Ltd. All rights reserved. Keywords: Schistosome; SVLBP; Schistosoma japonicum; LDL-ligand-binding cysteine-rich repeat; Low-density lipoprotein; Lipoprotein; Receptor  Sequences presented here have been assigned GenBank accession number AF091537. ∗ Corresponding author at Department of Tropical Medicine, SL-17, Tulane University, Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Tel.: +1-504-988-4645; fax: +1-504-988-6686. E-mail address: paul.brindley@tulane.edu (P.J. Brindley). 1357-2725/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S1357-2725(03)00105-5