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- EMDB-31839: Cryo-EM structure of Rat NTCP complexed with YN69202Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-31839
TitleCryo-EM structure of Rat NTCP complexed with YN69202Fab
Map data
Sample
  • Complex: Complex of NTCP and Fab
    • Complex: Fab
      • Protein or peptide: Fab heavy chain from antibody IgG clone number YN69202
      • Protein or peptide: Fab light chain from antibody IgG clone number YN69202
    • Complex: NTCP
      • Protein or peptide: Sodium/bile acid cotransporter
KeywordsHepatitis B virus (HBV) / host entry receptor / bile acid transporter / taurocholate / Na+-coupled symporter / TRANSPORT PROTEIN
Function / homology
Function and homology information


Recycling of bile acids and salts / bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid transmembrane transporter activity / bile acid and bile salt transport / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / basolateral plasma membrane ...Recycling of bile acids and salts / bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid transmembrane transporter activity / bile acid and bile salt transport / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / basolateral plasma membrane / response to ethanol / 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 speciesMus musculus (house mouse) / Rattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.11 Å
AuthorsAsami J / Shimizu T
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-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_31839.png

Downloads & links

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Map

FileDownload / File: emd_31839.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.25 Å/pix.
x 200 pix.
= 249. Å		1.25 Å/pix.
x 200 pix.
= 249. Å		1.25 Å/pix.
x 200 pix.
= 249. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.245 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.06858949 - 0.11300365
Average (Standard dev.)0.000018637309 (±0.0023798638)
SymmetrySpace group: 1
Details

EMDB XML:

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

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Supplemental data

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Sample components

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Entire : Complex of NTCP and Fab

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

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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: Mus musculus (house mouse)

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Supramolecule #2: Fab

SupramoleculeName: Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Rattus norvegicus (Norway rat)

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Supramolecule #3: NTCP

SupramoleculeName: NTCP / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3

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Macromolecule #1: Fab heavy chain from antibody IgG clone number YN69202

MacromoleculeName: Fab heavy chain from antibody IgG clone number YN69202
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 26.574695 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
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

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

MacromoleculeName: Fab light 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: 24.32399 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
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

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Macromolecule #3: Sodium/bile acid cotransporter

MacromoleculeName: Sodium/bile acid cotransporter / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 38.03752 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MEVHNVSAPF NFSLPPGFGH RATDKALSII LVLMLLLIML SLGCTMEFSK IKAHLWKPKG VIVALVAQFG IMPLAAFLLG KIFHLSNIE ALAILICGCS PGGNLSNLFT LAMKGDMNLS IVMTTCSSFS ALGMMPLLLY VYSKGIYDGD LKDKVPYKGI M ISLVIVLI ...String:
MEVHNVSAPF NFSLPPGFGH RATDKALSII LVLMLLLIML SLGCTMEFSK IKAHLWKPKG VIVALVAQFG IMPLAAFLLG KIFHLSNIE ALAILICGCS PGGNLSNLFT LAMKGDMNLS IVMTTCSSFS ALGMMPLLLY VYSKGIYDGD LKDKVPYKGI M ISLVIVLI PCTIGIVLKS KRPHYVPYIL KGGMIITFLL SVAVTALSVI NVGNSIMFVM TPHLLATSSL MPFSGFLMGY IL SALFQLN PSCRRTISME TGFANIQLCS TILNVTFPPE VIGPLFFFPL LYMIFQLAEG LLIIIIFRCY EKIKPPKDQT KIT ENLYFQ GDYKDDDDKH HHHHHHH

UniProtKB: Hepatic sodium/bile acid cotransporter

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

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

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Electron microscopy

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

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 142734
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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