Tusnády G E, Bakos E, Váradi A, Sarkadi B
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest.
FEBS Lett. 1997 Jan 27;402(1):1-3. doi: 10.1016/s0014-5793(96)01478-0.
A group of ATP-binding cassette (ABC) transporters, including the yeast cadmium transporter (YCF1), the mammalian multidrug resistance-associated protein (MRP), the multispecific organic anion transporter and its congener (MOAT and EBCR), as well as the sulfonylurea receptor (SUR), group into a subfamily by sequence comparison. We suggest that these MRP-related proteins are also characterized by a special, common membrane topology pattern. The most studied ABC transporters, the cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug resistance (MDR) proteins, were shown to contain a tandem repeat of six transmembrane helices, each set followed by an ATP-binding domain. According to the present study, in contrast to various membrane topology predictions proposed for the different MRP-related proteins, they all seem to have a CFTR/MDR-like core structure, and an additional, large, N-terminal hydrophobic region. This latter domain is predicted to contain 4-6 (most probably 5) transmembrane helices, and is occasionally glycosylated on the cell surface. Since all the MRP-related transporters were shown to interact with anionic compounds, the N-terminal membrane-bound domain may have a key role in these interactions.
一组ATP结合盒（ABC）转运蛋白，包括酵母镉转运蛋白（YCF1）、哺乳动物多药耐药相关蛋白（MRP）、多特异性有机阴离子转运蛋白及其同类物（MOAT和EBCR），以及磺脲类受体（SUR），通过序列比较归为一个亚家族。我们认为这些与MRP相关的蛋白质也具有一种特殊的、共同的膜拓扑结构模式。研究最多的ABC转运蛋白，囊性纤维化跨膜电导调节因子（CFTR）和多药耐药（MDR）蛋白，被证明含有六个跨膜螺旋的串联重复序列，每组后面跟着一个ATP结合结构域。根据本研究，与针对不同MRP相关蛋白提出的各种膜拓扑预测相反，它们似乎都具有CFTR/MDR样的核心结构，以及一个额外的、大的N端疏水区域。后一个结构域预计包含4 - 6个（很可能是5个）跨膜螺旋，并且偶尔在细胞表面被糖基化。由于所有与MRP相关的转运蛋白都被证明与阴离子化合物相互作用，N端膜结合结构域可能在这些相互作用中起关键作用。
