可视化药物-质子转运体从内向开放到阻塞状态的非线性变化。
Visualizing the nonlinear changes of a drug-proton antiporter from inward-open to occluded state.
机构信息
From the Division of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, 610041, China.
Shanghai Synchrotron Radiation Facility Science Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201204, China.
出版信息
Biochem Biophys Res Commun. 2021 Jan 1;534:272-278. doi: 10.1016/j.bbrc.2020.11.096. Epub 2020 Dec 3.
Drug-proton antiporters (DHA) play an important role in multi-drug resistance, utilizing the proton-motive force to drive the expulsion of toxic molecules, including antibiotics and drugs. DHA transporters belong to the major facilitator superfamily (MFS), members of which deliver substrates by utilizing the alternating access model of transport. However, the transport process is still elusive. Here, we report the structures of SotB, a member of DHA1 family (TCDB: 2.A.1.2) from Escherichia coli. Four crystal structures of SotB were captured in different conformations, including substrate-bound occluded, inward-facing, and inward-open states. Comparisons between the four structures reveal nonlinear rigid-body movements of alternating access during the state transition from inward-open to occluded conformation. This work not only reveals the conformational dynamics of SotB but also deepens our understanding of the alternating access mechanism of MFS transporters.
药物-质子反向转运蛋白（DHA）在多药耐药性中发挥重要作用，利用质子动力势将包括抗生素和药物在内的有毒分子排出。DHA 转运蛋白属于主要易化因子超家族（MFS），其成员通过利用转运的交替访问模型来输送底物。然而，运输过程仍然难以捉摸。在这里，我们报道了大肠杆菌中 DHA1 家族（TCDB：2.A.1.2）成员 SotB 的结构。SotB 的四个晶体结构以不同的构象被捕获，包括底物结合的闭塞、内向和内向开放状态。四个结构之间的比较揭示了在从内向开放到闭塞构象的状态转变过程中交替访问的非线性刚体运动。这项工作不仅揭示了 SotB 的构象动力学，还加深了我们对 MFS 转运蛋白交替访问机制的理解。
Zotero 插件