title: Characterization of a gene family encoding SEA (sea-urchin sperm protein, enterokinase and agrin)-domain proteins with lectin-like and heme-binding properties from Schistosoma japonicum.
abstract: BACKGROUND
  We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information.
  
  
  RESULTS
  Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin)-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10(-6) M) and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition.
  
  
  CONCLUSIONS
  The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation), and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan ; Department of Parasitology and Entomology, Faculty of Bioscience, Nnamdi Azikiwe University, Awka, Nigeria.
authors.forename: Evaristus Chibunna
authors.initials: EC
authors.lastname: Mbanefo
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan.
authors.forename: Mohammed Nasir
authors.initials: MN
authors.lastname: Shuaibu
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan.
authors.forename: Mahamoud Sama
authors.initials: MS
authors.lastname: Cherif
authors.affiliation: Laboratory on Technology for Parasitic Disease Prevention and Control, Jiangsu Institute of Parasitic Diseases, Meiyuan, Wuxi, People's Republic of China.
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, Kohrimoto, Kagoshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wakao
authors.affiliation: Department of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, Kohrimoto, Kagoshima, Japan ; SUDx-Biotec Corporation, Shiroyama, Kagoshima, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suda
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Sakamoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D018171:Agrin / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D004765:Enteropeptidase / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012549:Schistosoma japonicum / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D018171:Agrin; D015801:Helminth Proteins; D037102:Lectins; D006418:Heme; D004765:Enteropeptidase