Structure of MsbA from E-coli:: A homolog of the multidrug resistance ATP binding cassette (ABC) transporters (Retracted Article. See vol 314, pg 1875, 2006)
Structure of MsbA from E-coli:: A homolog of the multidrug resistance ATP binding cassette (ABC) transporters (Retracted Article. See vol 314, pg 1875, 2006)
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DOI：
10.1126/science.293.5536.1793
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发表时间：
2001-09-07
期刊：
影响因子：
56.9
通讯作者：
Roth, CB
中科院分区：
文献类型：
--
作者：
Chang, G;Roth, CB
多药耐药（MDR）是一个严重的医学问题，对疾病的治疗和新疗法的开发提出了重大挑战。与多药耐药性相关的ABC转运蛋白（MDR-ABC转运蛋白）将疏水药物和脂质从细胞膜的内小叶转运到外小叶。为了更好地阐明的“触发器”机制的基板运动的脂质双层的结构基础，我们已经确定了结构的脂质翻转酶MsbA从大肠杆菌的X-射线晶体学的分辨率为4.5埃。MsbA被组织为同源二聚体，每个亚基含有六个跨膜α-螺旋和一个核苷酸结合结构域。带电残基内衬中央室的不对称分布表明了MsbA和其他MDR-ABC转运蛋白转运底物的一般机制。MsbA的结构可以作为MDR-ABC转运蛋白的模型，该转运蛋白赋予癌细胞和感染性微生物多药耐药性。
Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the "flip-flop" mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane alpha -helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.