Defective anion transport activity of the abnormal band 3 in hereditary ovalocytic red blood cells
Defective anion transport activity of the abnormal band 3 in hereditary ovalocytic red blood cells
复制标题
遗传性卵形红细胞中异常带3的阴离子转运活性缺陷
作者：
A. E. Schofield;D. Reardon;M. Tanner
遗传性卵细胞增多症在美拉尼西亚和东南亚疟疾流行的一些地区很常见。这些红细胞在试管1和2中抵抗疟疾寄生虫的入侵，卵形细胞个体比正常3被寄生得更少。这是由于卵圆细胞红细胞4，5的刚性较大。有人认为东南亚卵细胞增多症是由于膜阴离子转运蛋白(带3)6，7的杂合存在。我们用聚合酶链式反应从一个印度来源的卵圆细胞中克隆了带3的异常互补DNADNA，发现了与正常蛋白的两个变化：点突变(Lys56-→Glu)和序列AFSPQVLAA的缺失(残基400-408)，但没有证据表明N-端延伸7。在东南亚卵圆细胞的异常带3中也发现了该缺失，这似乎与卵圆细胞红细胞的异常特性有关。我们在这里表明，异常卵母细胞带3的膜域结构发生了很大的变化，该蛋白在阴离子转运活性方面存在缺陷。红细胞转运特性的改变可能在卵圆细胞个体的副谷氨酸血症的减少中起作用。
HEREDITARY ovalocytosis is common in some areas of Melanesia and South East Asia where malaria is endemic. These red cells resist invasion by malarial parasites in vitro1,2 and ovalocytic individuals are less parasitized than normal3. This has been attributed to the greater rigidity of ovalocytic red cells4,5. It has been suggested that South East Asian ovalocytosis results from the heterozygous presence of an altered membrane anion transporter (band 3)6,7. We have used the polymerase chain reaction to clone the abnormal band 3 complementary DNA from an ovalocytic of Indian origin8 and found two changes from the normal protein: a point mutation (Lys56-→Glu) and the deletion of the sequence AFSPQVLAA (residues 400–408), but no evidence for an N-terminal extension7. The deletion is also found in the abnor-mal band 3 of South East Asian ovalocytes9 and seems to be responsible for the unusual properties of the ovalocytic red cell. We show here that the membrane domain of the abnormal ovalocyte band 3 has a substantially altered structure and that the protein is defective in anion transport activity. The changed transport properties of the red cells may have a role in the reduced para-sitaemia of ovalocytic individuals.