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-Structure paper
タイトル | Cooperative transport mechanism of human monocarboxylate transporter 2. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 2429, Year 2020 |
掲載日 | 2020年5月15日 |
著者 | Bo Zhang / Qiuheng Jin / Lizhen Xu / Ningning Li / Ying Meng / Shenghai Chang / Xiang Zheng / Jiangqin Wang / Yuan Chen / Dante Neculai / Ning Gao / Xiaokang Zhang / Fan Yang / Jiangtao Guo / Sheng Ye / |
PubMed 要旨 | Proton-linked monocarboxylate transporters (MCTs) must transport monocarboxylate efficiently to facilitate monocarboxylate efflux in glycolytically active cells, and transport monocarboxylate slowly ...Proton-linked monocarboxylate transporters (MCTs) must transport monocarboxylate efficiently to facilitate monocarboxylate efflux in glycolytically active cells, and transport monocarboxylate slowly or even shut down to maintain a physiological monocarboxylate concentration in glycolytically inactive cells. To discover how MCTs solve this fundamental aspect of intracellular monocarboxylate homeostasis in the context of multicellular organisms, we analyzed pyruvate transport activity of human monocarboxylate transporter 2 (MCT2). Here we show that MCT2 transport activity exhibits steep dependence on substrate concentration. This property allows MCTs to turn on almost like a switch, which is physiologically crucial to the operation of MCTs in the cellular context. We further determined the cryo-electron microscopy structure of the human MCT2, demonstrating that the concentration sensitivity of MCT2 arises from the strong inter-subunit cooperativity of the MCT2 dimer during transport. These data establish definitively a clear example of evolutionary optimization of protein function. |
リンク | Nat Commun / PubMed:32415067 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 Å |
構造データ | EMDB-30143, PDB-7bp3: |
由来 |
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キーワード | TRANSPORT PROTEIN / Monocarboxylate transporter 2 / Major facilitator superfamily / Cooperative transport |