Liu S C, Zhai S, Palek J, Golan D E, Amato D, Hassan K, Nurse G T, Babona D, Coetzer T, Jarolim P
Division of Hematology/Oncology, St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, MA 02135.
N Engl J Med. 1990 Nov 29;323(22):1530-8. doi: 10.1056/NEJM199011293232205.
Southeast Asian ovalocytosis is a form of hereditary elliptocytosis in which the red cells are rigid and resistant to malaria invasion. The underlying molecular defect is unknown.
We studied the red cells of 54 patients with ovalocytosis and 122 normal controls. We found that ovalocytes contain a structurally and functionally abnormal band 3 protein, the principal transmembrane protein of red cells. The structural lesion of ovalocyte band 3 was revealed by limited proteolytic cleavage of the protein, which produced fragments of abnormal size that were derived from the cytoplasmic domain of the protein. The structural lesion was present in all the subjects with ovalocytosis but none of the controls. This region of band 3 serves as the principal binding site for the membrane skeleton, a submembrane protein network composed of ankyrin, spectrin, actin, and protein 4.1. The structural defect is dominantly inherited, being tightly linked with the inheritance of ovalocytosis (the probability of linkage is in excess of 10 million to 1). Ovalocyte band 3 bound considerably more tightly than normal band 3 to ankyrin, which connects the membrane skeleton to the band 3 protein. This tight binding of ovalocyte band 3 to the underlying skeleton containing ankyrin was directly confirmed in intact cells by the finding that ovalocyte band 3 had markedly reduced lateral mobility in the membrane.
The red cells in Southeast Asian ovalocytosis carry a structurally and functionally abnormal band 3 protein. This molecular defect may underlie the increased rigidity of the red cells and their resistance to invasion by malaria parasites.
东南亚椭圆形红细胞增多症是遗传性椭圆形红细胞增多症的一种形式，其红细胞僵硬且对疟疾入侵具有抗性。潜在的分子缺陷尚不清楚。
我们研究了54例椭圆形红细胞增多症患者和122名正常对照者的红细胞。我们发现椭圆形红细胞含有一种结构和功能异常的带3蛋白，它是红细胞的主要跨膜蛋白。通过对该蛋白进行有限的蛋白水解切割揭示了椭圆形红细胞带3的结构病变，产生了大小异常的片段，这些片段源自该蛋白的胞质结构域。这种结构病变存在于所有椭圆形红细胞增多症患者中，但在对照者中均未发现。带3的这一区域是膜骨架的主要结合位点，膜骨架是由锚蛋白、血影蛋白、肌动蛋白和蛋白4.1组成的膜下蛋白网络。该结构缺陷为显性遗传，与椭圆形红细胞增多症的遗传紧密相关（连锁概率超过千万分之一）。椭圆形红细胞带3与将膜骨架连接到带3蛋白的锚蛋白的结合比正常带3紧密得多。通过发现椭圆形红细胞带3在膜中的横向移动性明显降低，在完整细胞中直接证实了椭圆形红细胞带3与含有锚蛋白的下层骨架的紧密结合。
东南亚椭圆形红细胞增多症患者的红细胞携带结构和功能异常的带3蛋白。这种分子缺陷可能是红细胞硬度增加及其对疟原虫入侵具有抗性的基础。
