Proton motive force mediates a reorientation of the cytosolic domains of the multidrug transporter LmrP
Proton motive force mediates a reorientation of the cytosolic domains of the multidrug transporter LmrP
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DOI：
10.1007/s00018-004-4298-2
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发表时间：
2004-10-01
影响因子：
8
通讯作者：
Vigano, C
中科院分区：
文献类型：
--
作者：
Gbaguidi, B;Mazurkiewicz, P;Vigano, C
来自乳酸乳球菌的LmrP是一种45-kDa的膜蛋白，其通过充当质子动力驱动的外排泵而赋予对多种亲脂性化合物的抗性。这项研究表明，质子动力和配体相互作用改变了细胞溶质色氨酸残基的亲水性淬灭剂的可及性。质子动力介导LmrP向外部介质的可及性增加，并导致更高的药物结合。来自胞质环的残基Asp（128）和Asp（68）参与质子动力介导的可及性变化。配体结合不改变蛋白质的可及性，但质子动力介导的重组是随后的可及性变化的先决条件，由配体结合介导。Asp（142）与其他膜嵌入的羧基残基合作，以促进构象变化，增加LmrP对亲水性淬灭剂的可及性。这种药物结合介导的重组可能与高亲和力和低亲和力药物结合位点之间的过渡有关，并且对于细胞外介质中的药物释放至关重要。
LmrP from Lactococcus lactis is a 45-kDa membrane protein that confers resistance to a wide variety of lipophilic compounds by acting as a proton motive force-driven efflux pump. This study shows that both the proton motive force and ligand interaction alter the accessibility of cytosolic tryptophan residues to a hydrophilic quencher. The proton motive force mediates an increase of LmrP accessibility toward the external medium and results in higher drug binding. Residues Asp(128) and Asp(68), from cytosolic loops, are involved in the proton motive force-mediated accessibility change. Ligand binding does not modify the protein accessibility, but the proton motive force-mediated restructuring is prerequisite for a subsequent accessibility change mediated by ligand binding. Asp(142) cooperates with other membrane-embedded carboxylic residues to promote a conformational change that increases LmrP accessibility toward the hydrophilic quencher. This drug binding-mediated reorganization may be related to the transition between the high- and low-affinity drug-binding sites and is crucial for drug release in the extracellular medium.