Human ZG16p recognizes pathogenic fungi through non-self polyvalent mannose in the digestive system
Human ZG16p recognizes pathogenic fungi through non-self polyvalent mannose in the digestive system
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DOI：
10.1093/glycob/cwr130
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发表时间：
2012-02-01
期刊：
影响因子：
4.3
通讯作者：
Hirabayashi, Jun
中科院分区：
文献类型：
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作者：
Tateno, Hiroaki;Yabe, Rikio;Hirabayashi, Jun
人酶原颗粒蛋白 16 (ZG16p) 含有 Jacalin 样凝集素结构域，但其聚糖结合特性尚未完全了解。在这里，我们通过最近开发的糖复合物微阵列筛选了 ZG16p 的聚糖结合特异性。 ZG16p 似乎表现出与α-和β-连接的甘露糖-聚丙烯酰胺-生物素探针的选择性结合。在使用额亲和层析的更多定量分析中，两种类型的多价甘露糖（即高密度甘露糖和酵母甘露聚糖）的解离常数分别确定为1.3和1.7μM。进化上保守的氨基酸 Asp151（参与 Jacalin 相关凝集素 (JRL) 之间的糖结合）的突变消除了与甘露糖的结合活性。通过免疫组织化学染色，在消化系统的粘液分泌细胞中，如腮腺的血清腺泡细胞、胰腺的腺泡细胞和肠道的杯状细胞中，特异性地检测到ZG16p。最后，我们证明 ZG16p 以多价甘露糖依赖性方式识别致病性念珠菌和马拉色菌。我们认为ZG16p是甘露糖特异性JRL的新成员，它通过消化系统中的非自多价甘露糖识别病原真菌。
Human zymogen granule protein 16 (ZG16p) contains a Jacalin-like lectin domain, although its glycan-binding properties are not fully understood. Here, we screened the glycan-binding specificity of ZG16p by recently developed glycoconjugate microarray. ZG16p appeared to exhibit selective binding to alpha- and beta-linked mannose-polyacrylamide-biotin probes. In more quantitative analysis using frontal affinity chromatography, dissociation constants to two types of polyvalent mannose, i.e. high-density mannose and yeast mannan, were determined to be 1.3 and 1.7 mu M, respectively. Mutation of the evolutionarily conserved amino acid Asp151, which is involved in sugar binding among the Jacalin-related lectins (JRLs), abolished binding activity to mannose. By immunohistochemical staining, ZG16p was specifically detected in mucus-secreting cells of the digestive system such as serosanguineous acinar cells of the parotid gland, acinar cells of the pancreas and goblet cells of the intestine. Finally, we showed that ZG16p recognizes pathogenic Candida and Malassezia species in a polyvalent mannose-dependent manner. We propose that ZG16p is a novel member of mannose-specific JRLs, which recognizes pathogenic fungi through non-self polyvalent mannose in the digestive system.