+Open data
-Basic information
Entry | Database: PDB / ID: 7vae | |||||||||
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Title | Cryo-EM structure of bovine NTCP complexed with YN69202Fab | |||||||||
Components |
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Keywords | TRANSPORT PROTEIN / Hepatitis B virus (HBV) / host entry receptor / bile acid transporter / taurocholate / Na+-coupled symporter | |||||||||
Function / homology | Function and homology information Recycling of bile acids and salts / bile acid:sodium symporter activity / bile acid and bile salt transport / membrane => GO:0016020 Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å | |||||||||
Authors | Asami, J. / Shimizu, T. / Ohto, U. | |||||||||
Funding support | Japan, 2items
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Citation | Journal: Nature / Year: 2022 Title: Structure of the bile acid transporter and HBV receptor NTCP. Authors: Jinta Asami / Kanako Terakado Kimura / Yoko Fujita-Fujiharu / Hanako Ishida / Zhikuan Zhang / Yayoi Nomura / Kehong Liu / Tomoko Uemura / Yumi Sato / Masatsugu Ono / Masaki Yamamoto / ...Authors: Jinta Asami / Kanako Terakado Kimura / Yoko Fujita-Fujiharu / Hanako Ishida / Zhikuan Zhang / Yayoi Nomura / Kehong Liu / Tomoko Uemura / Yumi Sato / Masatsugu Ono / Masaki Yamamoto / Takeshi Noda / Hideki Shigematsu / David Drew / So Iwata / Toshiyuki Shimizu / Norimichi Nomura / Umeharu Ohto / Abstract: Chronic infection with hepatitis B virus (HBV) affects more than 290 million people worldwide, is a major cause of cirrhosis and hepatocellular carcinoma, and results in an estimated 820,000 deaths ...Chronic infection with hepatitis B virus (HBV) affects more than 290 million people worldwide, is a major cause of cirrhosis and hepatocellular carcinoma, and results in an estimated 820,000 deaths annually. For HBV infection to be established, a molecular interaction is required between the large glycoproteins of the virus envelope (known as LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP), a sodium-dependent bile acid transporter from the blood to hepatocytes. However, the molecular basis for the virus-transporter interaction is poorly understood. Here we report the cryo-electron microscopy structures of human, bovine and rat NTCPs in the apo state, which reveal the presence of a tunnel across the membrane and a possible transport route for the substrate. Moreover, the cryo-electron microscopy structure of human NTCP in the presence of the myristoylated preS1 domain of LHBs, together with mutation and transport assays, suggest a binding mode in which preS1 and the substrate compete for the extracellular opening of the tunnel in NTCP. Our preS1 domain interaction analysis enables a mechanistic interpretation of naturally occurring HBV-insusceptible mutations in human NTCP. Together, our findings provide a structural framework for HBV recognition and a mechanistic understanding of sodium-dependent bile acid translocation by mammalian NTCPs. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7vae.cif.gz | 132.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7vae.ent.gz | 105.6 KB | Display | PDB format |
PDBx/mmJSON format | 7vae.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vae_validation.pdf.gz | 759.3 KB | Display | wwPDB validaton report |
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Full document | 7vae_full_validation.pdf.gz | 767.9 KB | Display | |
Data in XML | 7vae_validation.xml.gz | 26.3 KB | Display | |
Data in CIF | 7vae_validation.cif.gz | 38.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/va/7vae ftp://data.pdbj.org/pub/pdb/validation_reports/va/7vae | HTTPS FTP |
-Related structure data
Related structure data | 31838MC 7vadC 7vafC 7vagC 7wsiC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-11056 (Title: Structure of bile acid transporter NTCP / Data size: 8.6 TB Data #1: Raw movies for Human NTCP (Q261A) - YN69202Fab (EMD-31837, PDB 7VAD) [micrographs - multiframe] Data #2: Raw movies for Bovine NTCP (Q261A) - YN69202Fab (EMD-31838, PDB 7VAE) [micrographs - multiframe] Data #3: Raw movies for Rat NTCP (Q261A) - YN69202Fab (EMD-31839, PDB 7VAE) [micrographs - multiframe] Data #4: Raw movies for Human NTCP (Q261A) - YN69202Fab-myr-preS1 (EMD-31840, PDB 7VAF) [micrographs - multiframe] Data #5: Raw movies for Human NTCP (wildtype) - YN69202Fab (EMD-32759, PDB 7WSI) [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 38105.398 Da / Num. of mol.: 1 / Mutation: Q261A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: SLC10A1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q2KJ85 |
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#2: Antibody | Mass: 26574.695 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
#3: Antibody | Mass: 24323.990 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
-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 |
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 Details: 25 mM Hepes-NaOH, pH 7.5, 0.15 M NaCl, and 0.01% GDN | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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 | Electron dose: 61 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 65717 / Symmetry type: POINT |