Cooperative transport mechanism of human monocarboxylate transporter 2

• DOI: 10.1038/s41467-020-16334-1
• Publication Date: 2020-05-15T10:05:00Z
• 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
• Keywords: Monocarboxylate transporter; Efflux

Abstract Proton-linked monocarboxylate transporters (MCTs) must transport efficiently to facilitate efflux in glycolytically active cells, and slowly or even shut down maintain a physiological concentration inactive cells. To discover how MCTs solve this fundamental aspect of intracellular homeostasis the context multicellular organisms, we analyzed pyruvate activity human transporter 2 (MCT2). Here show that MCT2 exhibits steep dependence on substrate concentration. This property allows turn almost like switch, which is physiologically crucial operation cellular context. We further determined cryo-electron microscopy structure MCT2, demonstrating sensitivity arises from strong inter-subunit cooperativity dimer during transport. These data establish definitively clear example evolutionary optimization protein function.