+Open data
-Basic information
Entry | Database: PDB / ID: 7bp3 | ||||||
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Title | Cryo-EM structure of the human MCT2 | ||||||
Components | Monocarboxylate transporter 2 | ||||||
Keywords | TRANSPORT PROTEIN / Monocarboxylate transporter 2 / Major facilitator superfamily / Cooperative transport | ||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||
Authors | Zhang, B. / Jin, Q. / Zhang, X. / Guo, J. / Ye, S. | ||||||
Citation | Journal: Nat Commun / Year: 2020 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 |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7bp3.cif.gz | 142.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7bp3.ent.gz | 111.7 KB | Display | PDB format |
PDBx/mmJSON format | 7bp3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7bp3_validation.pdf.gz | 907.2 KB | Display | wwPDB validaton report |
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Full document | 7bp3_full_validation.pdf.gz | 913 KB | Display | |
Data in XML | 7bp3_validation.xml.gz | 26.6 KB | Display | |
Data in CIF | 7bp3_validation.cif.gz | 39.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bp/7bp3 ftp://data.pdbj.org/pub/pdb/validation_reports/bp/7bp3 | HTTPS FTP |
-Related structure data
Related structure data | 30143MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 53919.707 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC16A7, MCT2 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: O60669 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Monocarboxylate transporter 2 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot for 4 seconds before plunging |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 0.25 sec. / Electron dose: 82 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Movie frames/image: 32 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 302904 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 100909 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |