Pornillos Owen, Chen Yen-Ju, Chen Andy P, Chang Geoffrey
Department of Molecular Biology, The Scripps Institute, 10550 North Torrey Pines Road, CB-105, Jolla, CA 92037, USA.
Science. 2005 Dec 23;310(5756):1950-3. doi: 10.1126/science.1119776.
EmrE is a prototype of the Small Multidrug Resistance family of efflux transporters and actively expels positively charged hydrophobic drugs across the inner membrane of Escherichia coli. Here, we report the x-ray crystal structure, at 3.7 angstrom resolution, of one conformational state of the EmrE transporter in complex with a translocation substrate, tetraphenylphosphonium. Two EmrE polypeptides form a homodimeric transporter that binds substrate at the dimerization interface. The two subunits have opposite orientations in the membrane and adopt slightly different folds, forming an asymmetric antiparallel dimer. This unusual architecture likely confers unidirectionality to transport by creating an asymmetric substrate translocation pathway. On the basis of available structural data, we propose a model for the proton-dependent drug efflux mechanism of EmrE.
EmrE是外排转运蛋白小多药耐药家族的一个原型，可将带正电荷的疏水性药物主动排出大肠杆菌内膜。在此，我们报告了EmrE转运蛋白与转运底物四苯基鏻结合的一种构象状态的X射线晶体结构，分辨率为3.7埃。两个EmrE多肽形成一个同二聚体转运蛋白，在二聚化界面结合底物。两个亚基在膜中具有相反的方向，并且采用略有不同的折叠方式，形成一个不对称的反平行二聚体。这种不同寻常的结构可能通过创建一个不对称的底物转运途径赋予转运单向性。基于现有的结构数据，我们提出了EmrE质子依赖性药物外排机制的模型。
