[English] 日本語
Yorodumi
- EMDB-31837: Cryo-EM structure of human NTCP complexed with YN69202Fab -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-31837
TitleCryo-EM structure of human NTCP complexed with YN69202Fab
Map data
Sample
  • Complex: Complex of NTCP and Fab
    • Complex: NTCP:
      • Protein or peptide: Sodium/bile acid cotransporter
    • Complex: FabFragment antigen-binding
      • Protein or peptide: Fab heavy chain from antibody IgG clone number YN69202
      • Protein or peptide: Fab light chain from antibody IgG clone number YN69202
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
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) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.41 Å
AuthorsAsami J / Shimizu T / Ohto U
Funding support Japan, 2 items
OrganizationGrant numberCountry
Ministry of Education, Culture, Sports, Science and Technology (Japan)19H03164 Japan
Ministry of Education, Culture, Sports, Science and Technology (Japan)19H00976 Japan
CitationJournal: 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
DepositionAug 29, 2021-
Header (metadata) releaseMay 25, 2022-
Map releaseMay 25, 2022-
UpdateJul 13, 2022-
Current statusJul 13, 2022Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_31837.png

Downloads & links

-
Map

FileDownload / File: emd_31837.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.245 Å
Density
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.06799966 - 0.09223359
Average (Standard dev.)2.3600396e-05 (±0.0021893547)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 249.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : Complex of NTCP and Fab

EntireName: Complex of NTCP and Fab
Components
  • Complex: Complex of NTCP and Fab
    • Complex: NTCP:
      • Protein or peptide: Sodium/bile acid cotransporter
    • Complex: FabFragment antigen-binding
      • Protein or peptide: Fab heavy chain from antibody IgG clone number YN69202
      • Protein or peptide: Fab light chain from antibody IgG clone number YN69202

-
Supramolecule #1: Complex of NTCP and Fab

SupramoleculeName: Complex of NTCP and Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #2: NTCP:

SupramoleculeName: NTCP: / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)

-
Supramolecule #3: Fab

SupramoleculeName: Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3

-
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: 38.141832 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
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 TGCANVQLCS TILNVAFPPE VIGPLFFFPL LYMIFQLGEG LLLIAIFWCY EKFKTPKDKT KMI ENLYFQ GDYKDDDDKH HHHHHHH

-
Macromolecule #2: Fab heavy chain from antibody IgG clone number YN69202

MacromoleculeName: Fab heavy chain from antibody IgG clone number YN69202
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 26.574695 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: EVQLQQSGPE LVKPGASVKM SCKASGYTFT SYIIHWVKQK PGQGLEWIGY INPYNDGTKY NEKFKGKGTL TSDKSSSTAY MELSSLTSE DSAVYYCARS YYDGIPHYFD YWGQGTTLTV SSAKTTPPSV YPLAPGCGDT TGSSVTLGCL VKGYFPESVT V TWNSGSLS ...String:
EVQLQQSGPE LVKPGASVKM SCKASGYTFT SYIIHWVKQK PGQGLEWIGY INPYNDGTKY NEKFKGKGTL TSDKSSSTAY MELSSLTSE DSAVYYCARS YYDGIPHYFD YWGQGTTLTV SSAKTTPPSV YPLAPGCGDT TGSSVTLGCL VKGYFPESVT V TWNSGSLS SSVHTFPALL QSGLYTMSSS VTVPSSTWPS QTVTCSVAHP ASSTTVDKKL EPSGPISTIN PCPPCKECHK CP APNLEGG PS

-
Macromolecule #3: Fab light chain from antibody IgG clone number YN69202

MacromoleculeName: Fab light chain from antibody IgG clone number YN69202
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.32399 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DIVMTQSPSS LAVSAGEKVT MSCKSSQSLF NSRTRRNYLA WYQQKPGQSP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT ISSVQAEDL AVYYCKQSYY LLTFGAGTKL ELKRADAAPT VSIFPPSSEQ LTSGGASVVC FLNNFYPKDI NVKWKIDGSE R QNGVLNSW ...String:
DIVMTQSPSS LAVSAGEKVT MSCKSSQSLF NSRTRRNYLA WYQQKPGQSP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT ISSVQAEDL AVYYCKQSYY LLTFGAGTKL ELKRADAAPT VSIFPPSSEQ LTSGGASVVC FLNNFYPKDI NVKWKIDGSE R QNGVLNSW TDQDSKDSTY SMSSTLTLTK DEYERHNSYT CEATHKTSTS PIVKSFNRNE C

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
Details: 25 mM Hepes-NaOH, pH 7.5, 0.15 M NaCl, and 0.01% GDN
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 61.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 103174

+
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