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- PDB-7pqq: Structure of thermostabilised human NTCP in complex with Megabody 91 -
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Open data
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Basic information
Entry | Database: PDB / ID: 7pqq | ||||||
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Title | Structure of thermostabilised human NTCP in complex with Megabody 91 | ||||||
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![]() | MEMBRANE PROTEIN / bile acid transporter | ||||||
Function / homology | ![]() glucosidase complex / trehalose catabolic process / alpha,alpha-trehalase activity / bile acid:sodium symporter activity / glucosidase activity / regulation of bile acid secretion / bile acid and bile salt transport / Hydrolases; Glycosylases; Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds / bile acid signaling pathway / Recycling of bile acids and salts ...glucosidase complex / trehalose catabolic process / alpha,alpha-trehalase activity / bile acid:sodium symporter activity / glucosidase activity / regulation of bile acid secretion / bile acid and bile salt transport / Hydrolases; Glycosylases; Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds / 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 / DNA damage response / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Goutam, K. / Reyes, N. | ||||||
Funding support | European Union, 1items
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 96.2 KB | Display | ![]() |
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PDB format | ![]() | 66.9 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 13596MC ![]() 7pqgC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 36652.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Antibody | Mass: 101583.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The protein is a fusion with Lama Glama and Escherichia Coli K-12 as its natural source. Source: (gene. exp.) ![]() ![]() ![]() ![]() Variant (production host): It is a fusion protein having lama glama and Escherichia Coli K12 as the source. References: UniProt: P42592, Hydrolases; Glycosylases; Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: human NTCP complexed with Megabody 91 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 56.5 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 184768 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 39.62 Å2 | ||||||||||||||||||||||||
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