Higgins Matthew K, Bokma Evert, Koronakis Eva, Hughes Colin, Koronakis Vassilis
Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):9994-9. doi: 10.1073/pnas.0400375101. Epub 2004 Jun 28.
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 TolC 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-A-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.
革兰氏阴性菌中的多重耐药性是由三组分膜泵赋予的，这些膜泵能将多种抗生素排出细胞。这些外排泵由内膜转运蛋白（如AcrB质子反向转运蛋白）、TolC家族的外膜出口通道和一种称为衔接蛋白的周质蛋白组成。我们展示了来自人类病原体铜绿假单胞菌的MexA衔接蛋白的X射线结构。这个细长的分子包含三个线性排列的亚结构域；一个47埃长的α-螺旋发夹结构、一个硫辛酰结构域和一个六链β-桶状结构。在晶体中，相邻MexA单体的发夹结构并排堆积形成扭曲的弧。我们讨论了晶体中分子堆积的影响。基于该结构和堆积情况，我们提出了一个关于组装好的药物外排泵中外膜通道与衔接蛋白之间关键周质相互作用的模型。
