Structure of the periplasmic component of a bacterial drug efflux pump
Structure of the periplasmic component of a bacterial drug efflux pump
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DOI：
10.1073/pnas.0400375101
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发表时间：
2004-07-06
影响因子：
11.1
通讯作者：
Koronakis, V
中科院分区：
文献类型：
--
作者：
Higgins, MK;Bokma, E;Koronakis, V
革兰氏阴性细菌的多重耐药是由三组分膜泵赋予的，它将多种抗生素从细胞中排出。这些外排泵包括一个内膜转运体，如AcrB质子反转运体，一个ToIC家族的外膜出口管道，以及一个被称为适配器的质周蛋白。我们提出了从人类病原体铜绿假单胞菌MexA适配器的x射线结构。细长的分子包含三个线性排列的子结构域；一个47埃长的螺旋发夹，一个脂酰结构域，和一个六链β -桶。在晶体中，相邻的MexA单体的发夹并排排列，形成扭曲的弧形。我们讨论了分子在晶体内排列的含义。在结构和包装的基础上，我们提出了组装药物外排泵中外膜通道与衔接蛋白之间关键的质周相互作用的模型。
Multidrug resistance among Gram-negative bacteria is conferred by three-component membrane pumps that expel diverse antibiotics from the cell. These efflux pumps consist of an inner membrane transporter such as the AcrB proton antiporter, an outer membrane exit duct of the ToIC family, and a periplasmic protein known as the adaptor. We present the x-ray structure of the MexA adaptor from the human pathogen Pseudomonas aeruginosa. The elongated molecule contains three linearly arranged subdomains; a 47-Angstrom-long alpha-helical hairpin, a lipoyl domain, and a six-stranded beta-barrel. In the crystal, hairpins of neighboring MexA monomers pack side-by-side to form twisted arcs. We discuss the implications of the packing of molecules within the crystal. On the basis of the structure and packing, we suggest a model for the key periplasmic interaction between the outer membrane channel and the adaptor protein in the assembled drug efflux pump.