血型糖蛋白C是恶性疟原虫配体PfEBP-2(baebl)的红细胞膜受体

Glycophorin C is confirmed as the erythrocyte membrane receptor for one ligand of Plasmodium falciparum——Pf EBP-2(baebl)

恶性疟原虫(Plasmodium falciparum,Pf)红细胞结合蛋白-2(Pferythrocyte binding protein-2,PfEBP-2)是Duffy结合样红细胞结合蛋白(Duffy-binding-like erythrocyte-binding protein,DBL-EBP)家族的一个成员,长期以来Pf入侵人红细胞时该配体所需的受体迄未被确认。2003年Lobo等采用酶处理的红细胞与缺失不同膜表面蛋白的罕见变种红细胞,显示PfEBP-2不与缺失血型糖蛋白C(GPC)的红细胞结合,并且它与缺失外显子2或外显子3的GPC变种进行的结合亦互有差异,因此证明GPC是PfEBP-2(或称baebl,EBA-140)的红细胞膜受体。他们进一步检出GPC分子上的结合域局限在其外显子2的第14￣22位氨基酸残基范围。PfEBP-2与受体的相互作用需要唾液酸,而不涉及血型糖蛋白A(glycophorin A,GPA)或血型糖蛋白B(GPB),它代表了Pf入侵红细胞的一条新途径。Mayer等继续探索了BAEBL(VSTK)变种与GPC结合的特异性,揭示在该Pf配体变种的第II区,围绕Thr-121的两个Arg残基对保证BAEBL(VSTK)同唾液酸结合的特异反应十分关键。并认为,BAEBL的单个点突变将有助Pf识别各种红细胞表面糖蛋白或糖脂分子上的寡糖,从而显著拓宽了其入侵的范围。

PfEBP-2（Plasmodium falciparum erythrocyte binding protein-2） is a member of the Duffy-binding-like erythrocyte binding protein（DBL-EBP） family.However,it has not been clear in recent several decades about what receptor was required for this Pf ligand during its invasion of human erythrocytes.Taking advantage of a combination of enzymatically treated erythrocytes and rare variant erythrocytes lacking different membrane surface proteins,Lobo et al.in 2003 have revealed that PfEBP-2 does not bind to the red blood cells（RBCs） lacking glycophorin C（GPC）,but it binds differentially to GPC variants deficient in exon 2 or exon 3.Thus,GPC is identified as the erythrocyte membrane receptor of PfEBP-2（or called baebl,EBA-140）.They further assessed that the binding domain on GPC molecule is potentially restricted to the range of 14th to 22nd amino acid residues within exon 2.The interaction of PfEBP-2 with receptor is dependent upon the sialic acids and not involves GPA or GPB,therefore representing a novel route of invasion into the erythrocytes.Mayer and coworkers continued to investigate the binding specificity of GPC to one BAEBL variant（VSTK） and pointed out that two Arg residues surrounding Thr-121 in region II of Pf variant ligand are crucial for the specific interaction of BAEBL（VSTK） with the sialic acids.It is suggested that single-point mutations in BAEBL would be beneficial for Pf to recognize oligosaccharides on various erythrocyte surface glycoproteins or glycolipids,remarkably extending its scope of invasion.