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

Evaristus Chibunna Mbanefo,Mohammed Nasir Shuaibu,Mihoko Kikuchi,Yasuo Suda,Nguyen Tien Huy,Masahiro Wakao,Chuanxin Yu,Mahamoud Sama Cherif,Kenji Hirayama

doi:10.1371/journal.pntd.0002644

Abstract

BackgroundWe 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.Methodology/Principal FindingsHere, 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.ConclusionsThe 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.

Highlights

Schistosomiasis still ranks as the most important helminthic infection; second only to malaria in its socioeconomic burden in the resource constrained tropics and subtropics
Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism
While isolating membrane-bound and secreted proteins as targets for Schistosoma japonicum vaccine, we identified a novel potentially functional gene family which had originated by a gene duplication mechanism

Summary

Introduction

Schistosomiasis still ranks as the most important helminthic infection; second only to malaria in its socioeconomic burden in the resource constrained tropics and subtropics. It affects over 200 million people worldwide with more than 700 million people at risk of getting infected [1]. It is opined that a prophylactic alternative applied singly or in combination with other interventions, even with limited efficacy in limiting transmission is the optimum approach [2]. This intervention is especially needed in S. japonicum endemic areas, where non-human mammalian hosts are complicating control efforts. Many transcripts were identified, no homolog was readily identifiable from sequence information

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Discussion

Conclusion