Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state
|Corresponding Author||Chen，Ligong; Zhang，Xiaokang; Yan，Hanchi; Ye，Sheng|
|Joint first author||Xu，Binghong; Zhang，Mingfeng; Zhang，Bo; Chi，Wenna; Ma，Xiaomin|
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.
共同第一 ; Others
Cited Times [WOS]:0
|Document Type||Journal Article|
|Department||Cryo-Electron Microscopy Center|
1.Frontiers Science Center for Synthetic Biology (Ministry of Education),Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures,School of Life Sciences,Tianjin University,Tianjin,92 Weijin Road, Nankai District,300072,China
2.Laboratory of Cell Fate Control,School of Life Sciences,Westlake University,Hangzhou,310000,China
3.Life Sciences Institute,Zhejiang University,Hangzhou,Zhejiang,310058,China
4.School of Pharmaceutical Sciences,Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education),Tsinghua University,Beijing,100084,China
5.Cryo-EM Centre,Southern University of Science and Technology,Shenzhen,Guangdong,515055,China
6.Interdisciplinary Center for Brain Information,The Brain Cognition and Brain Disease Institute,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China
7.Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions,Shenzhen,Guangdong,518055,China
8.Faculty of Life and Health Sciences,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China
Xu，Binghong,Zhang，Mingfeng,Zhang，Bo,et al. Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state[J]. Cell Reports,2022,40(11).
Xu，Binghong.,Zhang，Mingfeng.,Zhang，Bo.,Chi，Wenna.,Ma，Xiaomin.,...&Ye，Sheng.(2022).Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state.Cell Reports,40(11).
Xu，Binghong,et al."Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state".Cell Reports 40.11(2022).
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