Structural Study on Human Red Cell Band 3 Protein, AE1.

人红细胞阴离子交换器1(AE1)的膜结构域是一种氯离子/碳酸根离子逆向转运蛋白。这种交换是血液中CO_2/O_2循环的关键步骤。尽管它们很重要，但关于AE1和AE(阴离子交换)家族的结构信息仍然非常有限。我们用电子显微镜和X射线衍射法解析了AE1膜结构域的三维结构，通过交联将其固定在向外开放的构象中。以二维阵列排列的AE1膜结构域二聚体的投影图谱与ClC-/H^+逆向转运蛋白ClC氯通道的原核同源物的投影图谱相似。在三维图中，在二聚体中心附近有V形密度，在距离二聚体中心较远的地方有稍微狭窄的V形星团。这些似乎是从相反的侧面插入到膜中的。CLC转运蛋白内部重复序列中的两对同源螺旋(螺旋B+C和J+K)的结构基序与简单结构域移动后的AE1密度很好地匹配。用高分辨率研究红细胞内阴离子交换的结构和功能关系，可以得到足够好的结果。

The membrane domain of human erythrocyte anion exchanger 1(AE1) works as a Cl^-/HCO_3^-antiporter. This exchange is a key step for CO_2/O_2 circulation in the blood. In spite of their importance, structural information about AE1 and the AE(Anion Exchanger) family is still very limited. We used the electron microscopy and the X-ray diffraction methods to solve the three-dimensional structure of the AE1 membrane domain, fixed in an outward-open conformation by cross-linking. A dimer of AE1 membrane domains packed in two-dimensional array showed a projection map similar to that of the prokaryotic homolog of ClC chloride channel, a Cl^-/H^+antiporter. In a three-dimensional map, there are V-shaped densities near the center of the dimer, and slightly narrower V-shaped clusters at a greater distance from the center of the dimer. These appear to be inserted into membrane from opposite sides. The structural motifs, two homologous pairs of helices in internal repeats of ClC transporter(helices B+C and J+K), are well fitted to those AE1 densities after simple domain movement. We could get good enough results with a high resolution for examining the structure and function relationship of the anion exchange in red blood cells.