Crystal structure of the anion exchanger domain of human erythrocyte band 3
Crystal structure of the anion exchanger domain of human erythrocyte band 3
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DOI：
10.1126/science.aaa4335
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发表时间：
2015-11-06
期刊：
影响因子：
56.9
通讯作者：
Iwata, So
中科院分区：
文献类型：
--
作者：
Arakawa, Takatoshi;Kobayashi-Yurugi, Takami;Iwata, So
阴离子交换器1（AE 1），也称为带3或SLC 4A 1，通过促进氯离子和碳酸氢根穿过红细胞质膜的交换，在从组织中去除二氧化碳中起关键作用。AE 1的同种型也存在于肾脏中。人AE 1的特定突变可引起几种类型的遗传性溶血性贫血和/或远端肾小管酸中毒。在这里，我们报告的带3阴离子交换域（AE 1（CTD））在3.5埃的晶体结构。该结构通过抑制剂锁定在面向外的开放构象中。将该结构与尿嘧啶转运蛋白UraA的向内构象的底物结合结构进行比较，使我们能够确定AE 1（CTD）中的阴离子结合位置，并提出一种可能的转运机制，可以解释为什么选择的突变会导致疾病。
Anion exchanger 1 (AE1), also known as band 3 or SLC4A1, plays a key role in the removal of carbon dioxide from tissues by facilitating the exchange of chloride and bicarbonate across the plasma membrane of erythrocytes. An isoform of AE1 is also present in the kidney. Specific mutations in human AE1 cause several types of hereditary hemolytic anemias and/or distal renal tubular acidosis. Here we report the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. The structure is locked in an outward-facing open conformation by an inhibitor. Comparing this structure with a substrate-bound structure of the uracil transporter UraA in an inward-facing conformation allowed us to identify the anion-binding position in the AE1(CTD), and to propose a possible transport mechanism that could explain why selected mutations lead to disease.