Energy coupling mechanisms of AcrB-like RND transporters  

作　　者：Xuejun C. Zhang Min Liu Lei Han 

机构地区：[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2]College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China

出　　处：《Biophysics Reports》2017年第4期73-84,共12页生物物理学报（英文版）

基　　金：We thank Dr. Torsten Juelich for linguistic assistance during the preparation of this manuscript. This work was supported by the Ministry of Science and Technology （China） （2015CB910104 to XCZ） and National Natural Science Foundation of China （31470745 to XCZ）,

摘　　要：Prokaryotic AcrB-like proteins belong to a family of transporters of the RND superfamily, and as main contributing factor to multidrug resistance pose a tremendous threat to future human health. A unique feature of AcrB transporters is the presence of two separate domains responsible for carrying substrate and generating energy. Significant progress has been made in elucidating the three-dimensional structures of the homo-trimer complexes of AcrB-like transporters, and a three-step functional rotation was identified for this class of transporters. However, the detailed mechanisms for the transduction of the substrate binding signal, as well as the energy coupling processes between the functionally distinct domains remain to be established. Here, we propose a model for the interdomain communication in AcrB that explains how the substrate binding signal from the substrate-carrier domain triggers pro- tonation in the transmembrane domain. Our model further provides a plausible mechanism that explains how protonation induces conformational changes in the substrate-carrier domain. We sum- marize the thermodynamic principles that govern the functional cycle of the AcrB trimer complex.Prokaryotic AcrB-like proteins belong to a family of transporters of the RND superfamily, and as main contributing factor to multidrug resistance pose a tremendous threat to future human health. A unique feature of AcrB transporters is the presence of two separate domains responsible for carrying substrate and generating energy. Significant progress has been made in elucidating the three-dimensional structures of the homo-trimer complexes of AcrB-like transporters, and a three-step functional rotation was identified for this class of transporters. However, the detailed mechanisms for the transduction of the substrate binding signal, as well as the energy coupling processes between the functionally distinct domains remain to be established. Here, we propose a model for the interdomain communication in AcrB that explains how the substrate binding signal from the substrate-carrier domain triggers pro- tonation in the transmembrane domain. Our model further provides a plausible mechanism that explains how protonation induces conformational changes in the substrate-carrier domain. We sum- marize the thermodynamic principles that govern the functional cycle of the AcrB trimer complex.

关 键 词：ACRB RND transporter Membrane potential 

分 类 号：Q257[生物学—细胞生物学]