STRUCTURAL MODEL OF ATP-BINDING PROTEINS ASSOCIATED WITH CYSTIC-FIBROSIS, MULTIDRUG RESISTANCE AND BACTERIAL TRANSPORT
STRUCTURAL MODEL OF ATP-BINDING PROTEINS ASSOCIATED WITH CYSTIC-FIBROSIS, MULTIDRUG RESISTANCE AND BACTERIAL TRANSPORT
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DOI：
10.1038/346362a0
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发表时间：
1990-07-26
期刊：
影响因子：
64.8
通讯作者：
HIGGINS, CF
中科院分区：
文献类型：
--
作者：
HYDE, SC;EMSLEY, P;HIGGINS, CF
转运系统的ATP结合盒（ABC）超家族现在包括30多种蛋白质，它们具有广泛的序列相似性和结构域组织（综述见参考文献1-3）。该超家族包括原核生物、细菌输出蛋白和真核蛋白的周质结合蛋白依赖性摄取系统，包括与肿瘤多药耐药相关的P-糖蛋白（MDR）、介导酵母a因子交配信息素输出的STE 6基因产物、与疟原虫氯喹耐药性有关的pfMDR以及囊性纤维化基因（CFTR）的产物。在这里，我们提出了一个三级结构模型的ATP结合盒的特点，这一类的运输系统，根据预测的二级结构之间的相似性，这个家庭的成员和以前确定的结构的腺苷酸激酶。该模型对运输和囊性纤维化的分子基础都有影响，并为进一步的实验提供了框架。
THE ATP-binding cassette (ABC) superfamily of transport systems now includes over thirty proteins that share extensive sequence similarity and domain organization (reviewed in refs 1–3). This superfamily includes the well characterized periplasmic binding protein-dependent uptake systems of prokaryotes, bacterial exporters, and eukaryotic proteins including the P-glycoprotein associated with multidrug resistance in tumours (MDR), the STE6 gene product that mediates export of yeast a-factor mating pheromone, pfMDR that is implicated in chloroquine resistance of the malarial parasite, and the product of the cystic fibrosis gene (CFTR). Here we present a tertiary structure model of the ATP-binding cassettes characteristic of this class of transport system, based on similarities between the predicted secondary structures of members of this family and the previously determined structure of adenylate kinase. This model has implications for both the molecular basis of transport and cystic fibrosis and provides a framework for further experimentation.