+Open data
-Basic information
Entry | Database: PDB / ID: 8q7c | ||||||
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Title | Cryo-EM structure of Adenovirus C5 hexon | ||||||
Components | Hexon protein | ||||||
Keywords | VIRUS / capsid protein / trimer | ||||||
Function / homology | Function and homology information T=25 icosahedral viral capsid / microtubule-dependent intracellular transport of viral material towards nucleus / host cell / viral capsid / symbiont entry into host cell / host cell nucleus / structural molecule activity Similarity search - Function | ||||||
Biological species | Human adenovirus 5 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
Authors | Zoll, S. / Dhillon, A. | ||||||
Funding support | Czech Republic, 1items
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Citation | Journal: J Virol / Year: 2024 Title: Structural insights into the interaction between adenovirus C5 hexon and human lactoferrin. Authors: Arun Dhillon / B David Persson / Alexander N Volkov / Hagen Sülzen / Alan Kádek / Petr Pompach / Sami Kereïche / Martin Lepšík / Katarina Danskog / Charlotte Uetrecht / Niklas Arnberg / Sebastian Zoll / Abstract: Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment ...Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily its N-terminal lactoferricin (Lfcin) region, interacting with hexon's hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development. IMPORTANCE: Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where ...IMPORTANCE: Our study delves into the structural aspects of adenovirus (AdV) infections, specifically HAdV-C5 in the respiratory epithelium. It uncovers the molecular details of a novel pathway where human lactoferrin (hLF) interacts with the major capsid protein, hexon, facilitating viral entry, and bypassing traditional receptors such as CAR and integrins. The study's cryo-EM structures reveal how hLF engages hexon, primarily through its N-terminal lactoferricin (Lfcin) region and hexon's hypervariable region 1 (HVR-1). Mutational analyses identify critical Lfcin contacts and other regions within hLF vital for hexon binding. This structural insight sheds light on HAdV-C5's mechanism of utilizing soluble hLF/Lfcin for cellular entry, holding promise for gene therapy and vaccine development advancements in adenovirus research. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8q7c.cif.gz | 656.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8q7c.ent.gz | 429.2 KB | Display | PDB format |
PDBx/mmJSON format | 8q7c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8q7c_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8q7c_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8q7c_validation.xml.gz | 81.2 KB | Display | |
Data in CIF | 8q7c_validation.cif.gz | 119.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q7/8q7c ftp://data.pdbj.org/pub/pdb/validation_reports/q7/8q7c | HTTPS FTP |
-Related structure data
Related structure data | 18212MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 108107.617 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Human adenovirus 5 / References: UniProt: P04133 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Ternary complex of adenovirus C5 hexon polypeptides / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Value: 0.324 MDa / Experimental value: NO |
Source (natural) | Organism: Human adenovirus 5 |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K2 IS (4k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 53396 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 166.96 Å2 | ||||||||||||||||||||||||
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