Carpentieri Andrea, Ratner Daniel M, Ghosh Sudip K, Banerjee Sulagna, Bushkin G Guy, Cui Jike, Lubrano Michael, Steffen Martin, Costello Catherine E, O'Keefe Barry, Robbins Phillips W, Samuelson John
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, MA 02118, USA.
Eukaryot Cell. 2010 Nov;9(11):1661-8. doi: 10.1128/EC.00166-10. Epub 2010 Sep 17.
Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man(5)GlcNAc(2)). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-phosphodiester-linked glycans recognized by an anti-proteophosphoglycan monoclonal antibody. Cyanovirin-N inhibits phagocytosis by E. histolytica trophozoites of mucin-coated beads, a surrogate assay for amebic virulence. For technical reasons, we used the plant lectin concanavalin A rather than cyanovirin-N to enrich secreted and membrane proteins for mass spectrometric identification. E. histolytica glycoproteins with occupied N-glycan sites include Gal/GalNAc lectins, proteases, and 17 previously hypothetical proteins. The latter glycoproteins, as well as 50 previously hypothetical proteins enriched by concanavalin A, may be vaccine targets as they are abundant and unique. In summary, the antiretroviral lectin cyanovirin-N binds to well-known and novel targets on the surface of E. histolytica that are rapidly replenished from large intracellular pools.
溶组织内阿米巴是一种可导致阿米巴痢疾和肝脓肿的原生生物,它具有一种由七个糖(Man(5)GlcNAc(2))组成的截短型N - 连接聚糖(N - 聚糖)前体。在此,我们发现,具有未修饰N - 聚糖的糖蛋白会在溶组织内阿米巴滋养体表面被抗逆转录病毒凝集素蓝藻抗病毒蛋白N聚集并封闭,然后从大量细胞内池得到补充。蓝藻抗病毒蛋白N会与半乳糖/ N - 乙酰半乳糖胺黏附凝集素以及含有被抗蛋白磷酸聚糖单克隆抗体识别的O - 磷酸二酯连接聚糖的糖蛋白共同封闭。蓝藻抗病毒蛋白N可抑制溶组织内阿米巴滋养体对黏蛋白包被珠子的吞噬作用,这是一种用于检测阿米巴毒力的替代试验。出于技术原因,我们使用植物凝集素伴刀豆球蛋白A而非蓝藻抗病毒蛋白N来富集分泌蛋白和膜蛋白以进行质谱鉴定。具有被占据N - 聚糖位点的溶组织内阿米巴糖蛋白包括半乳糖/ N - 乙酰半乳糖胺凝集素、蛋白酶以及17种先前的假设蛋白。后一类糖蛋白以及伴刀豆球蛋白A富集的50种先前的假设蛋白可能是疫苗靶点,因为它们丰富且独特。总之,抗逆转录病毒凝集素蓝藻抗病毒蛋白N可与溶组织内阿米巴表面的已知和新靶点结合,这些靶点可从大量细胞内池快速得到补充。