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Open data
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Basic information
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Title | Cryo-EM structure of human NTCP-myr-preS1-YN9048Fab complex | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Asami J / Shimizu T / Ohto U | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of hepatitis B virus receptor binding. Authors: Jinta Asami / Jae-Hyun Park / Yayoi Nomura / Chisa Kobayashi / Junki Mifune / Naito Ishimoto / Tomoko Uemura / Kehong Liu / Yumi Sato / Zhikuan Zhang / Masamichi Muramatsu / Takaji Wakita / ...Authors: Jinta Asami / Jae-Hyun Park / Yayoi Nomura / Chisa Kobayashi / Junki Mifune / Naito Ishimoto / Tomoko Uemura / Kehong Liu / Yumi Sato / Zhikuan Zhang / Masamichi Muramatsu / Takaji Wakita / David Drew / So Iwata / Toshiyuki Shimizu / Koichi Watashi / Sam-Yong Park / Norimichi Nomura / Umeharu Ohto / ![]() ![]() Abstract: Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. ...Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus-host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 81 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.2 KB 17.2 KB | Display Display | ![]() |
Images | ![]() | 68.8 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() | 80.9 MB 80.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hrxMC ![]() 8hryC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_34981_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_34981_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : NTCP-myr-preS1-YN9048Fab
Entire | Name: NTCP-myr-preS1-YN9048Fab |
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Components |
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-Supramolecule #1: NTCP-myr-preS1-YN9048Fab
Supramolecule | Name: NTCP-myr-preS1-YN9048Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-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: 38.198883 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 TGCQNVQLCS TILNVAFPPE VIGPLFFFPL LYMIFQLGEG LLLIAIFWCY EKFKTPKDKT KMI ENLYFQ GDYKDDDDKH HHHHHHH UniProtKB: Hepatic sodium/bile acid cotransporter |
-Macromolecule #2: PreS1 protein (Fragment)
Macromolecule | Name: PreS1 protein (Fragment) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 6.229594 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: GTNLSVPNPL GFFPDHQLDP AFKANSENPD WDLNPHKDNW PDANKVGDYK DDDDK UniProtKB: PreS1 protein |
-Macromolecule #3: Fab heavy chain from antibody IgG clone number YN9048
Macromolecule | Name: Fab heavy chain from antibody IgG clone number YN9048 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.410627 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: EVQLQESGPE LVKPGDSVKM SCKASGYTFT DYYMDWVKQN HGKSLEWIGY IYPYNGGTNY NQKFKGKATL TVDKSSSTAY MELHSLTSE DSAVYYCARR GRFPWLAYWG QGTLVTVSAA KTTPPSVYPL APGCGDTTGS SVTLGCLVKG YFPESVTVTW N SGSLSSSV ...String: EVQLQESGPE LVKPGDSVKM SCKASGYTFT DYYMDWVKQN HGKSLEWIGY IYPYNGGTNY NQKFKGKATL TVDKSSSTAY MELHSLTSE DSAVYYCARR GRFPWLAYWG QGTLVTVSAA KTTPPSVYPL APGCGDTTGS SVTLGCLVKG YFPESVTVTW N SGSLSSSV HTFPALLQSG LYTMSSSVTV PSSTWPSQTV TCSVAHPASS TTVDKKLEPS GPISTINPCP PCKECHKCPA PN LEGGPS |
-Macromolecule #4: Fab light chain from antibody IgG clone number YN9048
Macromolecule | Name: Fab light chain from antibody IgG clone number YN9048 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.83123 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: DIVMTQTTSS LSASLGDRVT ISCRASQDIS NYLNWYQQKP DGTVRVLIYY TSRLHSGVPS RFSGSGSGTD FSLTISNLEP EDIATYYCQ QYSKFPWTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIVMTQTTSS LSASLGDRVT ISCRASQDIS NYLNWYQQKP DGTVRVLIYY TSRLHSGVPS RFSGSGSGTD FSLTISNLEP EDIATYYCQ QYSKFPWTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 / Details: 25 mM HEPES-NaOH pH 7.5, 150 mM NaCl, 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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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 59.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.89 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 103000 |