National Natural Science Foundation of China (NSFC)
31971127 to S.Y., 31870742 and 32071216 to H.Y., 31600606 and 32161133022 to X.Z., 91857108 and 81470839 to L.C.
China
Citation
Journal: Cell Rep / Year: 2022 Title: Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state. Authors: 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 / ...Authors: 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 / Abstract: Cell-surface ancillary glycoproteins basigin or embigin form heterodimeric complexes with proton-coupled monocarboxylate transporters (MCTs), facilitating the membrane trafficking of MCTs and ...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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