A hydrophobic ligand-binding protein of the Taenia solium metacestode mediates uptake of the host lipid: implication for the maintenance of parasitic cellular homeostasis.
Parasitic organisms are incapable of de novo fatty acid synthesis due to a down-regulated expression of enzymes involved in the oxygen-dependent pathway. We investigated the uptake of host lipids by a 150-kDa hydrophobic ligand-binding protein (HLBP) of Taenia solium metacestode, an agent causative of neurocysticercosis. The protein was found to be a hetero-oligomeric complex consisting of multiple subunits (M(r) 7, 10, and 15 kDa within pH 8.0-9.7), which may originate from four unique genes of 7- and 10-kDa gene families with 2-3 polymorphic alleles/paralogs. The 15-kDa protein represented glycosylated forms of the 10-kDa. With high binding affinity to lipid analogs, these subunits evidenced high-level sequence identity with other cestode HLBPs and form a novel clade associated with excretory-secretory type HLBP. In vitro experiments with viable worms suggested that the excreted 150-kDa protein might bind to lipids, and participate in the translocation of host lipids across the syncytial membrane. This process was substantially inhibited by the specific anti-150 kDa antibodies. The protein was localized in the parasite syncytium and in the lipid droplets within host granuloma wall, where significant lipase activity was expressed. HLBP-mediated uptake of the host lipid may be critical for the parasite survival and thus could be targeted by chemotherapeutics and/or vaccine.
Lee
Eung-Goo
EG
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, Suwon, Korea.
Kim
Seon-Hee
SH
Bae
Young-An
YA
Chung
Joon-Yong
JY
Suh
Myungkoo
M
Na
Byoung-Kuk
BK
Kim
Tong-Soo
TS
Kang
Insug
I
Ma
Liang
L
Kong
Yoon
Y
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D020019:Neurocysticercosis / Q000209:etiology / Q000378:metabolism / Q000469:parasitology / Q000517:prevention & control; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D041201:Taenia solium / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity
D002352:Carrier Proteins; D015801:Helminth Proteins; D008024:Ligands