Tanner M J
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Mol Membr Biol. 1997 Oct-Dec;14(4):155-65. doi: 10.3109/09687689709048178.
This review discusses recent advances in our understanding of the structure, function and molecular genetics of the membrane domain of red cell anion exchanger, band 3 (AE1), and its role in red cell and kidney disease. A new model for the topology of band 3 has been proposed, which suggests the membrane domain has 12 membrane spans, rather than the 14 membrane spans of earlier models. The major difference between the models is in the topology of the region on the C-terminal side of membrane spans 1-7. Two dimensional crystals of the deglycosylated membrane domain of band 3 have yielded two and three dimensional projection maps of the membrane domain dimer at low resolution. The human band 3 gene has been completely sequenced and this has facilitated the study of natural band 3 mutations and their involvement in disease. About 20% of hereditary spherocytosis cases arise from heterozygosity for band 3 mutations, and result in the absence or decrease of the mutant protein in the red cell membrane. Several other natural band 3 mutations are known that appear to be clinically benign, but alter red cell phenotype or are associated with altered red cell blood group antigens. These include the mutant band 3 present in Southeast Asian ovalocytosis, a condition which provides protection against cerebral malaria in children. Familial distal renal tubular acidosis, a condition associated with kidney stones, has been shown to result from a novel group of band 3 mutations. The total absence of band 3 has been described in animals-occurring naturally in cattle and after targeted disruption in mice. Some of these severely anaemic animals survive, so band 3 is not strictly essential for life. Although the band 3-negative red cells were very unstable, they contained a normally-assembled red cell skeleton, suggesting that the bilayer of the normal red cell membrane is stabilized by band 3 interactions with membrane lipids, rather than by interactions with the spectrin skeleton.
本综述讨论了我们对红细胞阴离子交换蛋白带3（AE1）膜结构域的结构、功能和分子遗传学的最新认识，以及它在红细胞和肾脏疾病中的作用。一种新的带3拓扑模型已被提出，该模型表明膜结构域有12个跨膜片段，而非早期模型中的14个跨膜片段。这些模型之间的主要差异在于跨膜片段1-7 C端一侧区域的拓扑结构。带3去糖基化膜结构域的二维晶体已产生了低分辨率下膜结构域二聚体的二维和三维投影图。人类带3基因已被完全测序，这有助于对天然带3突变及其在疾病中的作用进行研究。约20%的遗传性球形红细胞增多症病例源于带3突变的杂合性，导致红细胞膜中突变蛋白缺失或减少。已知还有其他几种天然带3突变，它们似乎在临床上是良性的，但会改变红细胞表型或与红细胞血型抗原改变有关。这些包括东南亚椭圆形红细胞增多症中存在的突变带3，这种病症可保护儿童免受脑型疟疾。家族性远端肾小管酸中毒是一种与肾结石相关的病症，已被证明是由一组新的带3突变引起的。在动物中已描述了带3的完全缺失，在牛中自然发生，在小鼠中经靶向破坏后也会出现。这些严重贫血的动物中有一些存活了下来，因此带3并非生命所必需。尽管带3阴性的红细胞非常不稳定，但它们含有正常组装的红细胞骨架，这表明正常红细胞膜的双层结构是通过带3与膜脂的相互作用而稳定的，而非通过与血影蛋白骨架的相互作用。
