[English] 日本語
Yorodumi
- EMDB-53474: CryoEM structure of nanodisc-reconstituted human NTCP in complex ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-53474
TitleCryoEM structure of nanodisc-reconstituted human NTCP in complex with grafted NTCP_Nb1 and NabFab
Map data
Sample
  • Complex: Nanodisc-reconstituted structure of human NTCP in complex with grafted NTCP_Nb1 and NabFab
    • Organelle or cellular component: Sodium-taurocholate co-transporting polypeptide (NTCP)
      • Protein or peptide: Sodium/bile acid cotransporter
    • Organelle or cellular component: Nanobody-binding Fab fragment (NabFab)
      • Protein or peptide: NabFab - Heavy Chain
      • Protein or peptide: NabFab - Light Chain
    • Organelle or cellular component: Grafted Nanobody NTCP_Nb1
      • Protein or peptide: Grafted Nanobody NTCP_Nb1
  • Ligand: SODIUM ION
KeywordsSolute Carrier Protein / Bile salt transporter / HBV/ HDV receptor / Sodium-coupled transport / TRANSPORT PROTEIN
Function / homology
Function and homology information


bile acid:sodium symporter activity / bile acid transmembrane transporter activity / bile acid and bile salt transport / Recycling of bile acids and salts / response to nutrient levels / response to estrogen / cellular response to xenobiotic stimulus / virus receptor activity / response to ethanol / basolateral plasma membrane / plasma membrane
Similarity search - Function
Bile acid:sodium symporter/arsenical resistance protein Acr3 / Bile acid:sodium symporter / Sodium Bile acid symporter family / Sodium/solute symporter superfamily
Similarity search - Domain/homology
Hepatic sodium/bile acid cotransporter
Similarity search - Component
Biological speciesHomo sapiens (human) / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.11 Å
AuthorsYoon D / Nosol K / Rasouli A / Bang-Soerensen R / Irobalieva RN / Liu H / Tajkhorshid E / Locher KP
Funding support Switzerland, 1 items
OrganizationGrant numberCountry
Swiss National Science Foundation Switzerland
CitationJournal: Structure / Year: 2025
Title: Structure of nanobody-inhibited state of human bile salt transporter NTCP.
Authors: Daniel Yoon / Kamil Nosol / Ali Rasouli / Rose Bang-Sørensen / Rossitza N Irobalieva / Hongtao Liu / Emad Tajkhorshid / Kaspar P Locher /
Abstract: Sodium-taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter mediating the hepatic uptake of bile salts and serving as the receptor of hepatitis B and D viruses. While ...Sodium-taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter mediating the hepatic uptake of bile salts and serving as the receptor of hepatitis B and D viruses. While previous studies identified binding sites for sodium ions and substrates, the mechanism remains controversial. We here report a high-resolution structure of NTCP in a closed-tunnel conformation that does not feature substrate binding sites but reveals evidence of two bound sodium ions. To evaluate the functional relevance of this state and gain insight into the transport mechanism, we performed μs-scale molecular dynamics simulations of NTCP starting from distinct conformations and substrate and ion configurations. We observed that both the closed-tunnel and open-tunnel conformations are highly stable, but that the sodium ions and bile salt molecules can shift positions without substantial conformational changes. Our results suggest that the closed-tunnel conformation might represents an inactive state rather than an essential component of a productive transport cycle.
History
DepositionApr 23, 2025-
Header (metadata) releaseNov 5, 2025-
Map releaseNov 5, 2025-
UpdateNov 5, 2025-
Current statusNov 5, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_53474.png

Downloads & links

-
Map

FileDownload / File: emd_53474.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 384 pix.
= 248.832 Å		0.65 Å/pix.
x 384 pix.
= 248.832 Å		0.65 Å/pix.
x 384 pix.
= 248.832 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.648 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0087
Minimum - Maximum-0.04241467 - 0.061166327
Average (Standard dev.)0.000023209886 (±0.0013290981)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 248.832 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_53474_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_53474_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Nanodisc-reconstituted structure of human NTCP in complex with gr...

EntireName: Nanodisc-reconstituted structure of human NTCP in complex with grafted NTCP_Nb1 and NabFab
Components
  • Complex: Nanodisc-reconstituted structure of human NTCP in complex with grafted NTCP_Nb1 and NabFab
    • Organelle or cellular component: Sodium-taurocholate co-transporting polypeptide (NTCP)
      • Protein or peptide: Sodium/bile acid cotransporter
    • Organelle or cellular component: Nanobody-binding Fab fragment (NabFab)
      • Protein or peptide: NabFab - Heavy Chain
      • Protein or peptide: NabFab - Light Chain
    • Organelle or cellular component: Grafted Nanobody NTCP_Nb1
      • Protein or peptide: Grafted Nanobody NTCP_Nb1
  • Ligand: SODIUM ION

-
Supramolecule #1: Nanodisc-reconstituted structure of human NTCP in complex with gr...

SupramoleculeName: Nanodisc-reconstituted structure of human NTCP in complex with grafted NTCP_Nb1 and NabFab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #2: Sodium-taurocholate co-transporting polypeptide (NTCP)

SupramoleculeName: Sodium-taurocholate co-transporting polypeptide (NTCP)
type: organelle_or_cellular_component / ID: 2 / Parent: 1 / Macromolecule list: #1

-
Supramolecule #3: Nanobody-binding Fab fragment (NabFab)

SupramoleculeName: Nanobody-binding Fab fragment (NabFab) / type: organelle_or_cellular_component / ID: 3 / Parent: 1 / Macromolecule list: #2-#3

-
Supramolecule #4: Grafted Nanobody NTCP_Nb1

SupramoleculeName: Grafted Nanobody NTCP_Nb1 / type: organelle_or_cellular_component / ID: 4 / Parent: 1 / Macromolecule list: #4

-
Macromolecule #1: Sodium/bile acid cotransporter

MacromoleculeName: Sodium/bile acid cotransporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.149949 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEAHNASAPF NFTLPPNFGK RPTDLALSVI LVFMLFFIML SLGCTMEFSK IKAHLWKPKG LAIALVAQYG IMPLTAFVLG KVFRLKNIE ALAILVCGCS PGGNLSNVFS LAMKGDMNLS IVMTTCSTFC ALGMMPLLLY IYSRGIYDGD LKDKVPYKGI V ISLVLVLI ...String:
MEAHNASAPF NFTLPPNFGK RPTDLALSVI LVFMLFFIML SLGCTMEFSK IKAHLWKPKG LAIALVAQYG IMPLTAFVLG KVFRLKNIE ALAILVCGCS PGGNLSNVFS LAMKGDMNLS IVMTTCSTFC ALGMMPLLLY IYSRGIYDGD LKDKVPYKGI V ISLVLVLI PCTIGIVLKS KRPQYMRYVI KGGMIIILLC SVAVTVLSAI NVGKSIMFAM TPLLIATSSL MPFIGFLLGY VL SALFCLN GRCRRTVSME TGCQNVQLCS TILNVAFPPE VIGPLFFFPL LYMIFQLGEG LLLIAIFWCY EKFKTPKDKT KMI YTAATT EETIPGALGN GTYKGEDCSP CTA

UniProtKB: Hepatic sodium/bile acid cotransporter

-
Macromolecule #2: NabFab - Heavy Chain

MacromoleculeName: NabFab - Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.684463 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSYYSIHWV RQAPGKGLEW VAYISSSSSY TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARGYQYWQYH ASWYWNGGLD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV ...String:
EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSYYSIHWV RQAPGKGLEW VAYISSSSSY TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARGYQYWQYH ASWYWNGGLD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSCDKTH T

-
Macromolecule #3: NabFab - Light Chain

MacromoleculeName: NabFab - Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.258783 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String:
SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC

-
Macromolecule #4: Grafted Nanobody NTCP_Nb1

MacromoleculeName: Grafted Nanobody NTCP_Nb1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 15.233767 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QRQLVESGGG LVQPGGSLRL SCAASRFTFD DYTIGWFRQA PGKEREGVSY MSSRDGSTYY ADSVKGRFII SRDNVKNTVY LQMNSLEPE DTAVYYCAAA YRPWGLIGGN FDFSGAYWGK GTPVTVSSHH HHHHEPEA

-
Macromolecule #5: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 5 / Number of copies: 2
Molecular weightTheoretical: 22.99 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE-PROPANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 54.4 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 133506
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more