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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30143 | |||||||||
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Title | Cryo-EM structure of the human MCT2 | |||||||||
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![]() | Monocarboxylate transporter 2 / Major facilitator superfamily / Cooperative transport / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() pyruvate secondary active transmembrane transporter activity / pyruvate transmembrane transporter activity / lactate transmembrane transport / pyruvate transmembrane transport / monocarboxylic acid transmembrane transporter activity / lactate transmembrane transporter activity / monocarboxylic acid transport / Proton-coupled monocarboxylate transport / symporter activity / plasma membrane => GO:0005886 ...pyruvate secondary active transmembrane transporter activity / pyruvate transmembrane transporter activity / lactate transmembrane transport / pyruvate transmembrane transport / monocarboxylic acid transmembrane transporter activity / lactate transmembrane transporter activity / monocarboxylic acid transport / Proton-coupled monocarboxylate transport / symporter activity / plasma membrane => GO:0005886 / transport across blood-brain barrier / membrane => GO:0016020 / nucleoplasm / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Zhang B / Jin Q | |||||||||
![]() | ![]() Title: Cooperative transport mechanism of human monocarboxylate transporter 2. 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 / ![]() 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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 49.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12 KB 12 KB | Display Display | ![]() |
Images | ![]() | 41.4 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 551 KB | Display | ![]() |
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Full document | ![]() | 550.6 KB | Display | |
Data in XML | ![]() | 6.1 KB | Display | |
Data in CIF | ![]() | 6.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7bp3MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.8285 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Monocarboxylate transporter 2
Entire | Name: Monocarboxylate transporter 2 |
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Components |
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-Supramolecule #1: Monocarboxylate transporter 2
Supramolecule | Name: Monocarboxylate transporter 2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Monocarboxylate transporter 2
Macromolecule | Name: Monocarboxylate transporter 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 53.919707 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPPMPSAPPV HPPPDGGWGW IVVGAAFISI GFSYAFPKAV TVFFKEIQQI FHTTYSEIAW ISSIMLAVMY AGGPVSSVLV NKYGSRPVV IAGGLLCCLG MVLASFSSSV VQLYLTMGFI TGLGLAFNLQ PALTIIGKYF YRKRPMANGL AMAGSPVFLS S LAPFNQYL ...String: MPPMPSAPPV HPPPDGGWGW IVVGAAFISI GFSYAFPKAV TVFFKEIQQI FHTTYSEIAW ISSIMLAVMY AGGPVSSVLV NKYGSRPVV IAGGLLCCLG MVLASFSSSV VQLYLTMGFI TGLGLAFNLQ PALTIIGKYF YRKRPMANGL AMAGSPVFLS S LAPFNQYL FNTFGWKGSF LILGSLLLNA CVAGSLMRPL GPNQTTSKSK NKTGKTEDDS SPKKIKTKKS TWEKVNKYLD FS LFKHRGF LIYLSGNVIM FLGFFAPIIF LAPYAKDQGI DEYSAAFLLS VMAFVDMFAR PSVGLIANSK YIRPRIQYFF SFA IMFNGV CHLLCPLAQD YTSLVLYAVF FGLGFGSVSS VLFETLMDLV GAPRFSSAVG LVTIVECGPV LLGPPLAGKL VDLT GEYKY MYMSCGAIVV AASVWLLIGN AINYRLLAKE RKEENARQKT RESEPLSKSK HSEDVNVKVS NAQSVTSERE TNIVE GGSS GGWSHPQFEK UniProtKB: Monocarboxylate transporter 2 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 150 sec. / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 4 seconds before plunging. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average exposure time: 0.25 sec. / Average electron dose: 82.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-7bp3: |