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- PDB-8hrx: Cryo-EM structure of human NTCP-myr-preS1-YN9048Fab complex -

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Basic information

Entry
Database: PDB / ID: 8hrx
TitleCryo-EM structure of human NTCP-myr-preS1-YN9048Fab complex
Components
  • Fab heavy chain from antibody IgG clone number YN9048
  • Fab light chain from antibody IgG clone number YN9048
  • PreS1 protein (Fragment)
  • Sodium/bile acid cotransporter
KeywordsTRANSPORT PROTEIN / hepatitis / HBV
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)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.89 Å
AuthorsAsami, J. / Shimizu, T. / Ohto, U.
Funding support Japan, 1items
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, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 17, 2024Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed
Revision 1.2Apr 3, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Nov 6, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Sodium/bile acid cotransporter
B: PreS1 protein (Fragment)
H: Fab heavy chain from antibody IgG clone number YN9048
L: Fab light chain from antibody IgG clone number YN9048


Theoretical massNumber of molelcules
Total (without water)94,6704
Polymers94,6704
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Sodium/bile acid cotransporter


Mass: 38198.883 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NTCP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14973
#2: Protein PreS1 protein (Fragment)


Mass: 6229.594 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis B virus / Production host: Escherichia coli (E. coli) / References: UniProt: Q6RXR5
#3: Antibody Fab heavy chain from antibody IgG clone number YN9048


Mass: 26410.627 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Ondatra zibethicus (muskrat) / Production host: Mus musculus (house mouse)
#4: Antibody Fab light chain from antibody IgG clone number YN9048


Mass: 23831.230 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Ondatra zibethicus (muskrat) / Production host: Mus musculus (house mouse)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: NTCP-myr-preS1-YN9048Fab / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5 / Details: 25 mM HEPES-NaOH pH 7.5, 150 mM NaCl, 0.01% GDN
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 59 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: NONE
3D reconstructionResolution: 2.89 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 103000 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0036165
ELECTRON MICROSCOPYf_angle_d0.6298386
ELECTRON MICROSCOPYf_dihedral_angle_d3.928831
ELECTRON MICROSCOPYf_chiral_restr0.042959
ELECTRON MICROSCOPYf_plane_restr0.0041047

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