Molecular Basis for the p Phenotype
Molecular Basis for the p Phenotype
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p 表型的分子基础
DOI：
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发表时间：
2000
影响因子：
4.8
通讯作者：
Kazuro Furukawa
中科院分区：
文献类型：
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作者：
Keiko Furukawa;Koichi Iwamura;M. Uchikawa;B. N. Sojka;J. Wiels;T. Okajima;T. Urano;Kazuro Furukawa
p型个体缺乏p血型系统的Pk （Gb3）和p （Gb4）糖脂抗原。为了探讨这种表型的分子基础，我们分析了来自日本和瑞典的6个p表型个体的Gb3合成酶（α1,4-半乳糖转移酶；α1,4 gal - t）的DNA序列。在3个日本个体和1个瑞典p个体中分别发现了一个错义突变P251L和一个无义突变W261stop，在2个瑞典p个体中各发现了一个错义突变M183K和G187D，说明来自日本和瑞典的p个体在编码区存在明显的多个纯合点突变。转染表达载体对α 1,4gal - ts突变体进行功能分析，发现P251L和M183K突变完全丧失酶功能，W261stop和G187D突变产生边际活性。对α 1,4gal - t同源序列进行BLAST分析，发现存在错义突变的3个残基Met183、Gly187和Pro251在所有物种中高度保守，提示它们对α 1,4gal - t功能的重要性。
p phenotype individuals lack both Pk (Gb3) and P (Gb4) glycolipid antigens of the P blood group system. To explore the molecular basis for this phenotype, DNA sequences of Gb3 synthase (α1,4-galactosyltransferase; α1,4Gal-T) in six p phenotype individuals from Japan and Sweden were analyzed. A missense mutation P251L and a nonsense mutation W261stop in three and one Japanese indivuiduals, respectively, and missense mutations M183K and G187D in one each of two Swedish p individuals were found, indicating that p individuals from Japan and Sweden have distinct and multiple homozygous point mutations in the coding region. In the function analysis of the mutated α1,4Gal-Ts by the transfection of the expression vectors, P251L and M183K mutations showed complete loss of enzyme function, and W261stop and G187D mutations resulted in the marginal activity. BLAST analysis of homologous sequences of α1,4Gal-T revealed that three residues, Met183, Gly187, and Pro251, at which missense mutations were found, were highly conserved among all species examined, suggesting their importance for the function of α1,4Gal-T.