Ma Che, Chang Geoffrey
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB-105, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2852-7. doi: 10.1073/pnas.0400137101. Epub 2004 Feb 17.
Multidrug resistance efflux transporters threaten to reverse the progress treating infectious disease by extruding a wide range of drug and other cytotoxic compounds. One such drug transporter, EmrE, from the small multidrug resistance family, utilizes proton gradients as an energy source to drive substrate translocation. In an effort to understand the molecular structural basis of this transport mechanism, we have determined the structure of EmrE from Escherichia coli to 3.8 A. EmrE is a tetramer comprised of two conformational heterodimers related by a pseudo two-fold symmetry axis perpendicular to the cell membrane. Based on the structure and biochemical evidence, we propose a mechanism by which EmrE accomplishes multidrug efflux by coupling conformational changes between two heterodimers with proton gradient. Because of its simplicity and compact size, the structure of EmrE can serve as an ideal model for understanding the general structural basis of proton:drug antiport for other drug efflux systems.
多药耐药性外排转运蛋白可能会通过排出多种药物和其他细胞毒性化合物，使传染病治疗的进展发生逆转。来自小多药耐药家族的一种此类药物转运蛋白EmrE，利用质子梯度作为能量来源来驱动底物转运。为了理解这种转运机制的分子结构基础，我们已将大肠杆菌中的EmrE结构解析到3.8埃。EmrE是一个四聚体，由两个构象异源二聚体组成，这两个异源二聚体通过垂直于细胞膜的伪二重对称轴相关联。基于该结构和生化证据，我们提出了一种机制，即EmrE通过将两个异源二聚体之间的构象变化与质子梯度偶联来实现多药外排。由于其简单性和紧凑的尺寸，EmrE的结构可作为理解其他药物外排系统质子：药物反向转运一般结构基础的理想模型。
