描述人类溶酶体神经氨酸酶的定义存储障碍sialidosis代谢的分子基础。
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粗毛格子围巾E, van der Spoel, Fornerod M, Grosveld G、d 'Azzo
描述人类溶酶体神经氨酸酶的定义存储障碍sialidosis代谢的分子基础。
基因Dev。1996年12月15日,10 (24):3156 - 69。
- PubMed ID
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8985184 (在PubMed]
- 文摘
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神经氨酸苷酶(唾液酸酶)有重要作用的终端从sialoglycoconjugates唾液酸残基,在自然界中分布广泛。人类的溶酶体酶发生在复杂和保护性蛋白和β-半乳糖/组织蛋白酶(车牌提取),和缺乏两个遗传病:sialidosis,结构性缺陷引起的神经氨酸酶基因,和galactosialidosis,神经氨酸酶活动的损失是次要的车牌提取不足。我们发现了一个全长cDNA克隆数据库数据基础,预测的氨基酸序列具有广泛的同源性和细菌和其他哺乳动物神经氨酸苷酶,包括F (Y)把域和“Asp-boxes。”In situ hybridization localized the human neuraminidase gene to chromosome band 6p21, a region known to contain the HLA locus. Transient expression of the cDNA in deficient human fibroblasts showed that the enzyme is compartmentalized in lysosomes and restored neuraminidase activity in a PPCA-dependent manner. The authenticity of the cDNA was verified by the identification of three independent mutations in the open reading frame of the mRNA from clinically distinct sialidosis patients. Coexpression of the mutant cDNAs with PPCA failed to generate neuraminidase activity, confirming the inactivating effect of the mutations. These results establish the molecular basis of sialidosis in these patients, and clearly identify the cDNA-encoded protein as lysosomal neuraminidase.