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题名

Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state

作者
通讯作者Chen,Ligong; Zhang,Xiaokang; Yan,Hanchi; Ye,Sheng
共同第一作者Xu,Binghong; Zhang,Mingfeng; Zhang,Bo; Chi,Wenna; Ma,Xiaomin
发表日期
2022-09-13
DOI
发表期刊
EISSN
2211-1247
卷号40期号:11
摘要

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.

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共同第一 ; 其他
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被引频次[WOS]:6
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/402390
专题南方科技大学
冷冻电镜中心
作者单位
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
推荐引用方式
GB/T 7714
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).
APA
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).
MLA
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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