THE ANK REPEATS OF ERYTHROCYTE ANKYRIN FORM 2 DISTINCT BUT COOPERATIVE BINDING-SITES FOR THE ERYTHROCYTE ANION-EXCHANGER
THE ANK REPEATS OF ERYTHROCYTE ANKYRIN FORM 2 DISTINCT BUT COOPERATIVE BINDING-SITES FOR THE ERYTHROCYTE ANION-EXCHANGER
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DOI：
10.1074/jbc.270.37.22050
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发表时间：
1995-09-15
影响因子：
4.8
通讯作者：
BENNETT, V
中科院分区：
文献类型：
--
作者：
MICHAELY, P;BENNETT, V
锚蛋白的膜结合区的24个ANK重复形成四个折叠的亚域，每个亚域有六个ANK重复。这四个重复亚域至少与七个不同的膜蛋白家族相互作用。在红细胞中，锚定蛋白的主要膜靶标是Cl-/HCO3-阴离子交换器。这份报告首次证明了锚蛋白含有两个独立的阴离子交换二聚体结合位点。一个站点使用重复子域2(重复7-12)，而另一个站点需要重复子域3和4(重复13-24)。这两个地点的希尔系数为1.4，呈正相关。由于阴离子交换器以二聚体的形式存在于膜上，因此在锚蛋白上存在两个结合部位，使得锚蛋白可以同时与四个阴离子交换器相互作用。这些发现直接证明了ANK重复序列在蛋白质识别中的多功能性，并对红细胞和其他细胞中Ankyrin连接的完整膜蛋白的组织具有重要意义。
The 24 ANK repeats of the membrane-binding domain of ankyrin form four folded subdomains of six ANK repeats each. These four repeat subdomains mediate interactions with at least seven different families of membrane proteins. In the erythrocyte, the main membrane target of ankyrin is the Cl-/HCO3- anion exchanger. This report presents the first evidence that ankyrin contains two separate binding sites for anion exchanger dimers. One site utilizes repeat subdomain two (repeats 7-12) while the other requires both repeat subdomains three and four (repeats 13-24). The two sites are positively coupled with a Hill coefficient of 1.4. Since the anion exchanger exists as a dimer in the membrane, the presence of two binding sites on ankyrin allows ankyrin to interact with four anion exchangers simultaneously. These findings provide a direct demonstration of the versatility of ANK repeats in protein recognition, and have important implications for the organization of ankyrin-linked integral membrane proteins in erythrocytes as well as other cells.