Substrate-bound structure of the E. coli multidrug resistance transporter MdfA, Cell Researchadvance online publication 4 August 2015
发布时间：2015年08月11日
Cell Research, advance online publication 4 August 2015; doi: 10.1038/cr.2015.94
Substrate-bound structure of the E. coli multidrug resistance transporter MdfA
Jie Heng1,2, Yan Zhao1,3, Ming Liu4, Yue Liu1, Junping Fan1, Xianping Wang1, Yongfang Zhao1 and Xuejun C Zhang1
1National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
3School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China
4College of Biotechnology, Tianjin University of Science and Technology, 29 13th Street, TEDA, Tianjin 300457, China
Correspondence: Yongfang Zhao, E-mail: yongfangzhao@ibp.ac.cn; Xuejun C Zhang, E-mail: zhangc@ibp.ac.cn
Abstract Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes at resolutions up to 2.0 angstrom, all in the inward-facing conformation. The substrate-binding site sits proximal to the conserved acidic residue, D34. Our mutagenesis studies support the structural observations of the substrate-binding mode and the notion that D34 responds to substrate binding by adjusting its protonation status. Taken together, our data unveil the substrate-binding mode of MFS antiporters and suggest a mechanism of transport via this group of transporters.
附件下载：
Substrate-bound structure of the E. coli multidrug resistance transporter MdfA, Cell Research advance online publication 4 August 2015
Cell Research, advance online publication 4 August 2015; doi: 10.1038/cr.2015.94
Substrate-bound structure of the E. coli multidrug resistance transporter MdfA
Jie Heng1,2, Yan Zhao1,3, Ming Liu4, Yue Liu1, Junping Fan1, Xianping Wang1, Yongfang Zhao1 and Xuejun C Zhang1
1National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
3School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China
4College of Biotechnology, Tianjin University of Science and Technology, 29 13th Street, TEDA, Tianjin 300457, China
Correspondence: Yongfang Zhao, E-mail: yongfangzhao@ibp.ac.cn; Xuejun C Zhang, E-mail: zhangc@ibp.ac.cn
Abstract
Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes at resolutions up to 2.0 angstrom, all in the inward-facing conformation. The substrate-binding site sits proximal to the conserved acidic residue, D34. Our mutagenesis studies support the structural observations of the substrate-binding mode and the notion that D34 responds to substrate binding by adjusting its protonation status. Taken together, our data unveil the substrate-binding mode of MFS antiporters and suggest a mechanism of transport via this group of transporters.
文章链接：http://dx.doi.org/10.1038/cr.2015.94
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