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- EMDB-34981: Cryo-EM structure of human NTCP-myr-preS1-YN9048Fab complex -

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Basic information

Entry
Database: EMDB / ID: EMD-34981
TitleCryo-EM structure of human NTCP-myr-preS1-YN9048Fab complex
Map data
Sample
  • Complex: NTCP-myr-preS1-YN9048Fab
    • Protein or peptide: Sodium/bile acid cotransporter
    • Protein or peptide: PreS1 protein (Fragment)
    • Protein or peptide: Fab heavy chain from antibody IgG clone number YN9048
    • Protein or peptide: Fab light chain from antibody IgG clone number YN9048
Keywordshepatitis / HBV / TRANSPORT PROTEIN
Function / homology
Function and homology information


bile acid:sodium symporter activity / membrane fusion involved in viral entry into host cell / 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 ...bile acid:sodium symporter activity / membrane fusion involved in viral entry into host cell / 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 / symbiont entry into host cell / virion attachment to host cell / virion membrane / plasma membrane
Similarity search - Function
Large envelope protein S / Major surface antigen from hepadnavirus / 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 / PreS1 protein
Similarity search - Component
Biological speciesHomo sapiens (human) / Hepatitis B virus / Ondatra zibethicus (muskrat)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.89 Å
AuthorsAsami J / Shimizu T / Ohto U
Funding support Japan, 1 items
OrganizationGrant numberCountry
Ministry of Education, Culture, Sports, Science and Technology (Japan)22H02556 Japan
CitationJournal: Nat Struct Mol Biol / Year: 2024
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
DepositionDec 16, 2022-
Header (metadata) releaseJan 17, 2024-
Map releaseJan 17, 2024-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_34981.png

Downloads & links

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Map

FileDownload / File: emd_34981.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 300 pix.
= 249. Å		0.83 Å/pix.
x 300 pix.
= 249. Å		0.83 Å/pix.
x 300 pix.
= 249. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.005
Minimum - Maximum-0.01658245 - 0.026199888
Average (Standard dev.)0.0000045095867 (±0.0005935831)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 249.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_34981_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_34981_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : NTCP-myr-preS1-YN9048Fab

EntireName: NTCP-myr-preS1-YN9048Fab
Components
  • Complex: NTCP-myr-preS1-YN9048Fab
    • Protein or peptide: Sodium/bile acid cotransporter
    • Protein or peptide: PreS1 protein (Fragment)
    • Protein or peptide: Fab heavy chain from antibody IgG clone number YN9048
    • Protein or peptide: Fab light chain from antibody IgG clone number YN9048

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Supramolecule #1: NTCP-myr-preS1-YN9048Fab

SupramoleculeName: NTCP-myr-preS1-YN9048Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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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: 38.198883 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 TGCQNVQLCS TILNVAFPPE VIGPLFFFPL LYMIFQLGEG LLLIAIFWCY EKFKTPKDKT KMI ENLYFQ GDYKDDDDKH HHHHHHH

UniProtKB: Hepatic sodium/bile acid cotransporter

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Macromolecule #2: PreS1 protein (Fragment)

MacromoleculeName: PreS1 protein (Fragment) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Hepatitis B virus
Molecular weightTheoretical: 6.229594 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
GTNLSVPNPL GFFPDHQLDP AFKANSENPD WDLNPHKDNW PDANKVGDYK DDDDK

UniProtKB: PreS1 protein

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Macromolecule #3: Fab heavy chain from antibody IgG clone number YN9048

MacromoleculeName: Fab heavy chain from antibody IgG clone number YN9048 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Ondatra zibethicus (muskrat)
Molecular weightTheoretical: 26.410627 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: 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

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Macromolecule #4: Fab light chain from antibody IgG clone number YN9048

MacromoleculeName: Fab light chain from antibody IgG clone number YN9048 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Ondatra zibethicus (muskrat)
Molecular weightTheoretical: 23.83123 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: 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

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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, 150 mM NaCl, 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: 59.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
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: 2.89 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 103000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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