Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state
Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state
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Embigin 促进单羧酸转运蛋白 1 定位至质膜并转变为解偶联状态
DOI：
10.1016/j.celrep.2022.111343
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Sheng Ye
中科院分区：
文献类型：
--
作者：
Binghong Xu;Mingfeng Zhang;Bo Zhang;Wenna Chi;Xiaomin Ma;Wei Zhang;Minmin Dong;Linlin Sheng;Yi Zhang;Wenhao Jiao;Yuanyue Shan;Wenjing Chang;Peiyi Wang;Shiheng Wen;Duanqing Pei;Ligong Chen;Xiaokang Zhang;Hanchi Yan;Sheng Ye
细胞表面辅助糖蛋白basigin或embigin与质子偶联单羧酸转运蛋白（MCT）形成异二聚体复合物，促进MCT的膜运输并调节其转运活性。在这里，我们确定了冷冻电子显微镜（cryo-EM）结构的人MCT 1-embigin复合物，并观察到embigin形成广泛的相互作用与MCT 1，以促进其定位到质膜。此外，异二聚体的形成通过空间位阻效应有效地阻断了MCT 1形成同二聚体，释放了两个特征基序之间的偶联，并驱动了MCT跨膜螺旋5（TM 5）的显著构象变化。因此，底物结合口袋在同二聚体偶联状态和异二聚体去耦状态之间交替，并表现出底物结合亲和力的差异，支持以下假设：源自MCT二聚体一个亚基的底物诱导运动可传递至相邻亚基以改变其底物结合亲和力。
Cell-surface ancillary glycoproteins basigin or embigin form heterodimeric complexes with proton-coupled monocarboxylate transporters (MCTs), facilitating the membrane trafficking of MCTs and regulating their transport activities. Here, we determine the cryoelectron microscopy (cryo-EM) structure of the human MCT1-embigin complex and observe that embigin forms extensive interactions with MCT1 to facilitate its localization to the plasma membrane. In addition, the formation of the heterodimer effectively blocks MCT1 from forming a homodimer through a steric hindrance effect, releasing the coupling between two signature motifs and driving a significant conformation change in transmembrane helix 5 (TM5) of MCTs. Consequently, the substrate-binding pocket alternates between states of homodimeric coupling and heterodimeric decoupling states and exhibits differences in substrate-binding affinity, supporting the hypothesis that the substrate-induced motion originating in one subunit of the MCT dimer could be transmitted to the adjacent subunit to alter its substrate-binding affinity.