7BP3

Cryo-EM structure of the human MCT2

Summary for 7BP3

• Entry DOI: 10.2210/pdb7bp3/pdb
• EMDB information: 30143
• Descriptor: Monocarboxylate transporter 2 (1 entity in total)
• Functional Keywords: monocarboxylate transporter 2, major facilitator superfamily, cooperative transport, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 107839.41

Authors

Zhang, B.,Jin, Q.,Zhang, X.,Guo, J.,Ye, S. (deposition date: 2020-03-21, release date: 2020-06-03, Last modification date: 2024-03-27)

Primary citation

Zhang, B.,Jin, Q.,Xu, L.,Li, N.,Meng, Y.,Chang, S.,Zheng, X.,Wang, J.,Chen, Y.,Neculai, D.,Gao, N.,Zhang, X.,Yang, F.,Guo, J.,Ye, S.
Cooperative transport mechanism of human monocarboxylate transporter 2.
Nat Commun, 11:2429-2429, 2020

PubMed Abstract: 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.

PubMed: 32415067
DOI: 10.1038/s41467-020-16334-1

Experimental method

ELECTRON MICROSCOPY (3.8 Å)