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Yorodumi- PDB-7pqg: Structure of thermostabilised human NTCP in complex with nanobody 87 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7pqg | ||||||
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Title | Structure of thermostabilised human NTCP in complex with nanobody 87 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / SLC10A1 / sodium bile acid symporter | ||||||
Function / homology | Function and homology information bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid and bile salt transport / bile acid signaling pathway / Recycling of bile acids and salts / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / virus receptor activity ...bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid and bile salt transport / bile acid signaling pathway / Recycling of bile acids and salts / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / virus receptor activity / basolateral plasma membrane / response to ethanol / plasma membrane Similarity search - Function | ||||||
Biological species | Lama glama (llama) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Goutam, K. / Reyes, N. | ||||||
Funding support | European Union, 1items
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Citation | Journal: Nature / Year: 2022 Title: Structural basis of sodium-dependent bile salt uptake into the liver. Authors: Kapil Goutam / Francesco S Ielasi / Els Pardon / Jan Steyaert / Nicolas Reyes / Abstract: The liver takes up bile salts from blood to generate bile, enabling absorption of lipophilic nutrients and excretion of metabolites and drugs. Human Na-taurocholate co-transporting polypeptide (NTCP) ...The liver takes up bile salts from blood to generate bile, enabling absorption of lipophilic nutrients and excretion of metabolites and drugs. Human Na-taurocholate co-transporting polypeptide (NTCP) is the main bile salt uptake system in liver. NTCP is also the cellular entry receptor of human hepatitis B and D viruses (HBV/HDV), and has emerged as an important target for antiviral drugs. However, the molecular mechanisms underlying NTCP transport and viral receptor functions remain incompletely understood. Here we present cryo-electron microscopy structures of human NTCP in complexes with nanobodies, revealing key conformations of its transport cycle. NTCP undergoes a conformational transition opening a wide transmembrane pore that serves as the transport pathway for bile salts, and exposes key determinant residues for HBV/HDV binding to the outside of the cell. A nanobody that stabilizes pore closure and inward-facing states impairs recognition of the HBV/HDV receptor-binding domain preS1, demonstrating binding selectivity of the viruses for open-to-outside over inward-facing conformations of the NTCP transport cycle. These results provide molecular insights into NTCP 'gated-pore' transport and HBV/HDV receptor recognition mechanisms, and are expected to help with development of liver disease therapies targeting NTCP. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7pqg.cif.gz | 82.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pqg.ent.gz | 62.3 KB | Display | PDB format |
PDBx/mmJSON format | 7pqg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7pqg_validation.pdf.gz | 639.1 KB | Display | wwPDB validaton report |
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Full document | 7pqg_full_validation.pdf.gz | 653.4 KB | Display | |
Data in XML | 7pqg_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | 7pqg_validation.cif.gz | 25.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pq/7pqg ftp://data.pdbj.org/pub/pdb/validation_reports/pq/7pqg | HTTPS FTP |
-Related structure data
Related structure data | 13593MC 7pqqC 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 |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Antibody | Mass: 14988.481 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Strain: Lama glama / Variant: 9844 / Production host: Escherichia coli K-12 (bacteria) / Strain (production host): WK6 |
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#2: Protein | Mass: 36652.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC10A1, NTCP, GIG29 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q14973 |
-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: Human NTCP in complex with nanobody 87 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||
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: 57.8 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 61053 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 156.22 Å2 | ||||||||||||||||||||||||
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