A molecular defect of spectrin in a subset of patients with hereditary elliptocytosis. Alterations in the alpha-subunit domain involved in spectrin self-association.
A molecular defect of spectrin in a subset of patients with hereditary elliptocytosis. Alterations in the alpha-subunit domain involved in spectrin self-association.
复制标题
遗传性椭圆红细胞增多症患者亚群中血影蛋白的分子缺陷。
DOI：
10.1172/jci111376
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Prchal,J
中科院分区：
文献类型：
--
作者：
Lawler,J;Liu,SC;Palek,J;Prchal,J
遗传性椭圆形红细胞增多症（HE）是一组临床和生化异质性疾病，其特征是椭圆形红细胞和常染色体显性遗传方式。而血影蛋白异源二聚体与四聚体的自缔合在HE患者亚群中是有缺陷的，称为HE[SpD-SpD]，在其他人中是正常的。我们已经研究了有限的胰蛋白酶消化血影蛋白提取物与HE患者[SpD-SpD]，以确定血影蛋白的自我关联的功能缺陷是否可以与血影蛋白分子的结构变化产生的肽模式。虽然有限的胰蛋白酶消化血影蛋白提取物产生的肽模式与正常对照志愿者血影蛋白提取物的模式是无法区分的，消化的血影蛋白提取物从HE[SpD-SpD]患者显示了一个可再现的减少在80,000-D域的α-亚基，这是参与血影蛋白二聚体的自我缔合。在9个家系中，8个家系中80，000-D片段的减少与74，000-D片段的增加相关，或者在一个家系中，46，000和17，000 D片段的增加相关。这些非典型的肽模式是类似的遗传性焦斑红细胞症（HPP），也有缺陷的自关联血影蛋白的两个变种先前报道的。这些数据表明血影蛋白α亚基的两种不同结构变体与HE患者亚群中有缺陷的血影蛋白异源二聚体自缔合相关。
Hereditary elliptocytosis (HE) is a clinically and biochemically heterogenous group of diseases characterized by elliptically shaped erythrocytes and an autosomal dominant mode of inheritance. Whereas the self-association of spectrin heterodimers to tetramers is defective in a subpopulation of HE patients, designated HE[SpD-SpD], it is normal in others. We have examined the peptide pattern produced by limited tryptic digestion of spectrin extracts from patients with HE[SpD-SpD] to determine if the functional defects in spectrin self-association could be correlated with structural changes in the spectrin molecule. Although the peptide pattern produced by limited tryptic digestion of spectrin extracts from those HE patients with normal spectrin self-association was indistinguishable from the pattern from control normal volunteers, digestion of the spectrin extracts from the HE[SpD-SpD] patients showed a reproducible diminution in the 80,000-D domain of the alpha-subunit, which is involved in spectrin dimer self-association. The decrease in the 80,000-D fragment was associated with an increase in a 74,000-D fragment in eight of nine families, or, in one family, with an increase of fragments at 46,000 and 17,000 D. These atypical peptide patterns were similar to those previously reported in two variants of hereditary pyropoikilocytosis (HPP), which also had defective self-association of spectrin. These data indicate that two distinct structural variants of spectrin alpha-subunit are associated with the defective spectrin heterodimer self-association in a subpopulation of HE patients.Images