Covitz K M, Panagiotidis C H, Hor L I, Reyes M, Treptow N A, Shuman H A
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
EMBO J. 1994 Apr 1;13(7):1752-9. doi: 10.1002/j.1460-2075.1994.tb06439.x.
The maltose transport system of Escherichia coli is a well-characterized member of the ATP binding cassette transporter superfamily. Members of this family share sequence similarity surrounding two short sequences (the Walker A and B sequences) which constitute a nucleotide binding pocket. It is likely that the energy from binding and hydrolysis of ATP is used to accomplish the translocation of substrate from one location to another. Periplasmic binding protein-dependent transport systems, like the maltose transport system of E.coli, possess a water-soluble ligand binding protein that is essential for transport activity. In addition to delivering ligand to the membrane-bound components of the system on the external face of the membrane, the interaction of the binding protein with the membrane complex initiates a signal that is transmitted to the ATP binding subunit on the cytosolic side and stimulates its hydrolytic activity. Mutations that alter the membrane complex so that it transports independently of the periplasmic binding protein also result in constitutive activation of the ATPase. Genetic analysis indicates that, in general, two mutations are required for binding protein-independent transport and constitutive ATPase. The mutations alter residues that cluster to specific regions within the membrane spanning segments of the integral membrane components MalF and MalG. Individually, the mutations perturb the ability of MBP to interact productively with the membrane complex. Genetic alteration of this signalling pathway suggests that other agents might have similar effects. These could be potentially useful for modulating the activities of ABC transporters such as P-glycoprotein or CFTR, that are implicated in disease.
大肠杆菌的麦芽糖转运系统是ATP结合盒转运蛋白超家族中一个特征明确的成员。该家族成员在构成核苷酸结合口袋的两个短序列（沃克A序列和沃克B序列）周围具有序列相似性。ATP结合和水解产生的能量可能用于完成底物从一个位置到另一个位置的转运。像大肠杆菌的麦芽糖转运系统一样，周质结合蛋白依赖性转运系统拥有一种水溶性配体结合蛋白，它对转运活性至关重要。除了将配体递送至膜外侧的系统膜结合组分外，结合蛋白与膜复合物的相互作用引发一个信号，该信号传递至胞质侧的ATP结合亚基并刺激其水解活性。改变膜复合物使其独立于周质结合蛋白进行转运的突变也会导致ATP酶的组成型激活。遗传分析表明，一般来说，不依赖结合蛋白的转运和组成型ATP酶需要两个突变。这些突变改变了聚集在整合膜组分MalF和MalG跨膜区段内特定区域的残基。单独来看，这些突变扰乱了麦芽糖结合蛋白（MBP）与膜复合物有效相互作用的能力。该信号通路的基因改变表明其他因子可能有类似作用。这些可能对调节ABC转运蛋白如与疾病相关的P-糖蛋白或囊性纤维化跨膜传导调节因子（CFTR）的活性有潜在用途。
