+Open data
-Basic information
Entry | Database: PDB / ID: 6vqr | ||||||
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Title | CryoEM Structure of the PfFNT-inhibitor complex | ||||||
Components | Formate-nitrite transporter | ||||||
Keywords | MEMBRANE PROTEIN / Transporter | ||||||
Function / homology | Function and homology information high-affinity secondary active nitrite transmembrane transporter activity / lactate transmembrane transport / nitrite transport / lactate:proton symporter activity / plasma membrane Similarity search - Function | ||||||
Biological species | Plasmodium falciparum (malaria parasite P. falciparum) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.78 Å | ||||||
Authors | Su, C.C. / Lyu, M. | ||||||
Citation | Journal: EMBO Rep / Year: 2021 Title: Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT. Authors: Meinan Lyu / Chih-Chia Su / James W Kazura / Edward W Yu / Abstract: The intra-erythrocyte stage of P. falciparum relies primarily on glycolysis to generate adenosine triphosphate (ATP) and the energy required to support growth and reproduction. Lactic acid, a ...The intra-erythrocyte stage of P. falciparum relies primarily on glycolysis to generate adenosine triphosphate (ATP) and the energy required to support growth and reproduction. Lactic acid, a metabolic byproduct of glycolysis, is potentially toxic as it lowers the pH inside the parasite. Plasmodium falciparum formate-nitrite transporter (PfFNT), a 34-kDa transmembrane protein, has been identified as a novel drug target as it exports lactate from inside the parasite to the surrounding parasitophorous vacuole within the erythrocyte cytosol. The structure and detailed molecular mechanism of this membrane protein are not yet available. Here we present structures of PfFNT in the absence and presence of the functional inhibitor MMV007839 at resolutions of 2.56 Å and 2.78 Å using single-particle cryo-electron microscopy. Genetic analysis and transport assay indicate that PfFNT is able to transfer lactate across the membrane. Combined, our data suggest a stepwise displacement mechanism for substrate transport. The PfFNT membrane protein is capable of picking up lactate ions from the parasite's cytosol, converting them to lactic acids and then exporting these acids into the extracellular space. | ||||||
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 | 6vqr.cif.gz | 245.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vqr.ent.gz | 202.3 KB | Display | PDB format |
PDBx/mmJSON format | 6vqr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vqr_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6vqr_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6vqr_validation.xml.gz | 46.2 KB | Display | |
Data in CIF | 6vqr_validation.cif.gz | 66.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vq/6vqr ftp://data.pdbj.org/pub/pdb/validation_reports/vq/6vqr | HTTPS FTP |
-Related structure data
Related structure data | 21355MC 6vqqC 7mxyC 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: 34492.281 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Plasmodium falciparum (isolate 3D7) (eukaryote) Strain: isolate 3D7 / Gene: PF3D7_0316600 / Production host: Homo sapiens (human) / References: UniProt: O77389 #2: Chemical | ChemComp-R7M / ( Has ligand of interest | Y | |
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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: PfFNT / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Plasmodium falciparum 3D7 (eukaryote) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse. |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 29 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_3736: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.78 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141224 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | ||||||||||||||||||||||||
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