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Open data
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Basic information
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Title | Cryo-EM structure of human NTCP complexed with YN69202Fab | |||||||||
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Function / homology | ![]() 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.41 Å | |||||||||
![]() | Asami J / Shimizu T / Ohto U | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 23.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.8 KB 13.8 KB | Display Display | ![]() |
Images | ![]() | 54.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vadMC ![]() 7vaeC ![]() 7vafC ![]() 7vagC ![]() 7wsiC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
EM raw data | ![]() Data #1: Raw movies for Human NTCP (Q261A) - YN69202Fab (EMD-31837, PDB 7VAD) [micrographs - multiframe] Data #2: Raw movies for Bovine NTCP (Q261A) - YN69202Fab (EMD-31838, PDB 7VAE) [micrographs - multiframe] Data #3: Raw movies for Rat NTCP (Q261A) - YN69202Fab (EMD-31839, PDB 7VAE) [micrographs - multiframe] Data #4: Raw movies for Human NTCP (Q261A) - YN69202Fab-myr-preS1 (EMD-31840, PDB 7VAF) [micrographs - multiframe] Data #5: Raw movies for Human NTCP (wildtype) - YN69202Fab (EMD-32759, PDB 7WSI) [micrographs - multiframe]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.245 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Complex of NTCP and Fab
Entire | Name: Complex of NTCP and Fab |
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Components |
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-Supramolecule #1: Complex of NTCP and Fab
Supramolecule | Name: Complex of NTCP and Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: NTCP:
Supramolecule | Name: NTCP: / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Supramolecule #3: Fab
Supramolecule | Name: Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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-Macromolecule #1: Sodium/bile acid cotransporter
Macromolecule | Name: Sodium/bile acid cotransporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.141832 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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
Macromolecule | Name: Fab heavy chain from antibody IgG clone number YN69202 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.574695 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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
Macromolecule | Name: Fab light chain from antibody IgG clone number YN69202 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.32399 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 Details: 25 mM Hepes-NaOH, pH 7.5, 0.15 M NaCl, and 0.01% GDN |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 61.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 103174 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |