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-Structure paper
Title | Cooperative transport mechanism of human monocarboxylate transporter 2. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 2429, Year 2020 |
Publish date | May 15, 2020 |
Authors | 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 Abstract | 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. |
External links | Nat Commun / PubMed:32415067 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.8 Å |
Structure data | EMDB-30143, PDB-7bp3: |
Source |
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Keywords | TRANSPORT PROTEIN / Monocarboxylate transporter 2 / Major facilitator superfamily / Cooperative transport |