Visualizing the nonlinear changes of a drug-proton antiporter from inward-open to occluded state.
Visualizing the nonlinear changes of a drug-proton antiporter from inward-open to occluded state.
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DOI：
10.1016/j.bbrc.2020.11.096
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发表时间：
2020-12
影响因子：
3.1
通讯作者：
Q. Xiao;Bo Sun;Yanxia Zhou;Chen Wang;Li Guo;Jianhua He;D. Deng
中科院分区：
文献类型：
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作者：
Q. Xiao;Bo Sun;Yanxia Zhou;Chen Wang;Li Guo;Jianhua He;D. Deng
药物质子反向转运蛋白（DHA）在多药耐药中起着重要作用，它利用质子动力来驱动包括抗生素和药物在内的有毒分子的排出。DHA转运蛋白属于主要易化剂超家族（MFS），其成员通过利用交替进入转运模型递送底物。然而，运输过程仍然难以捉摸。本文报道了大肠杆菌DHA1家族（TCDB：2.A.1.2）成员SotB的结构。SotB的四种晶体结构被捕获在不同的构象，包括基板结合闭塞，面向内，和向内开放的状态。四种结构之间的比较揭示了非线性刚体运动的交替访问期间的状态转变，从内向开放的闭塞构象。这不仅揭示了SotB的构象动力学，也加深了我们对MFS转运蛋白交替进入机制的理解。
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) fromEscherichia 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.