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- PDB-8qk3: Human Adenovirus type 11 fiber knob in complex with its cell rece... -

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Basic information

Entry
Database: PDB / ID: 8qk3
TitleHuman Adenovirus type 11 fiber knob in complex with its cell receptors, Desmoglein-2 and CD46
Components
  • Desmoglein-2
  • Fiber protein
  • Membrane cofactor protein
KeywordsVIRAL PROTEIN / adenovirus / cell entry / receptor binding
Function / homology
Function and homology information


sequestering of extracellular ligand from receptor / inner acrosomal membrane / Purkinje myocyte development / positive regulation of protein localization to cell-cell junction / bundle of His cell-Purkinje myocyte adhesion involved in cell communication / cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication / desmosome organization / negative regulation of endothelial cell differentiation / negative regulation of complement activation, classical pathway / Keratinization ...sequestering of extracellular ligand from receptor / inner acrosomal membrane / Purkinje myocyte development / positive regulation of protein localization to cell-cell junction / bundle of His cell-Purkinje myocyte adhesion involved in cell communication / cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication / desmosome organization / negative regulation of endothelial cell differentiation / negative regulation of complement activation, classical pathway / Keratinization / positive regulation of transforming growth factor beta production / T cell mediated immunity / negative regulation of inflammatory response to wounding / desmosome / regulation of Notch signaling pathway / mesenchymal to epithelial transition / Formation of the cornified envelope / cornified envelope / regulation of ventricular cardiac muscle cell action potential / positive regulation of memory T cell differentiation / Apoptotic cleavage of cell adhesion proteins / adhesion receptor-mediated virion attachment to host cell / positive regulation of regulatory T cell differentiation / negative regulation of epithelial to mesenchymal transition / positive regulation of sprouting angiogenesis / homophilic cell-cell adhesion / positive regulation of stem cell population maintenance / regulation of heart rate by cardiac conduction / positive regulation of interleukin-10 production / intercalated disc / RHOG GTPase cycle / lateral plasma membrane / complement activation, classical pathway / RAC2 GTPase cycle / maternal process involved in female pregnancy / RAC3 GTPase cycle / single fertilization / cell adhesion molecule binding / positive regulation of T cell proliferation / positive regulation of cell adhesion / response to progesterone / Regulation of Complement cascade / stem cell proliferation / cell-cell adhesion / cell-cell junction / cell junction / viral capsid / signaling receptor activity / virus receptor activity / adaptive immune response / cell adhesion / apical plasma membrane / cadherin binding / negative regulation of gene expression / innate immune response / focal adhesion / intracellular membrane-bounded organelle / calcium ion binding / positive regulation of gene expression / symbiont entry into host cell / negative regulation of apoptotic process / host cell nucleus / cell surface / extracellular space / extracellular exosome / plasma membrane / cytoplasm
Similarity search - Function
Membrane cofactor protein CD46 / Desmosomal cadherin / : / : / Adenoviral fibre protein, repeat/shaft region / Adenoviral fibre protein, knob / Adenoviral fibre protein (knob domain) / Adenoviral fibre protein (repeat/shaft region) / Adenovirus fibre protein / Catenin binding domain superfamily ...Membrane cofactor protein CD46 / Desmosomal cadherin / : / : / Adenoviral fibre protein, repeat/shaft region / Adenoviral fibre protein, knob / Adenoviral fibre protein (knob domain) / Adenoviral fibre protein (repeat/shaft region) / Adenovirus fibre protein / Catenin binding domain superfamily / Attachment protein shaft domain superfamily / Adenovirus pIV-like, attachment domain / Cadherin conserved site / Cadherin domain signature. / Cadherin repeats. / Cadherin domain / Cadherin-like / Cadherins domain profile. / Cadherin-like superfamily / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily
Similarity search - Domain/homology
Membrane cofactor protein / Fiber protein / Desmoglein-2
Similarity search - Component
Biological speciesHuman adenovirus 11
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsEffantin, G.
Funding support France, 1items
OrganizationGrant numberCountry
Agence Nationale de la Recherche (ANR)ANR-18-CE11-0001 France
CitationJournal: J Virol / Year: 2023
Title: Toward the understanding of DSG2 and CD46 interaction with HAdV-11 fiber, a super-complex analysis.
Authors: Gregory Effantin / Marc-André Hograindleur / Daphna Fenel / Pascal Fender / Emilie Vassal-Stermann /
Abstract: The main limitation of oncolytic vectors is neutralization by blood components, which prevents intratumoral administration to patients. Enadenotucirev, a chimeric HAdV-11p/HAdV-3 adenovirus ...The main limitation of oncolytic vectors is neutralization by blood components, which prevents intratumoral administration to patients. Enadenotucirev, a chimeric HAdV-11p/HAdV-3 adenovirus identified by bio-selection, is a low seroprevalence vector active against a broad range of human carcinoma cell lines. At this stage, there's still some uncertainty about tropism and primary receptor utilization by HAdV-11. However, this information is very important, as it has a direct influence on the effectiveness of HAdV-11-based vectors. The aim of this work is to determine which of the two receptors, DSG2 and CD46, is involved in the attachment of the virus to the host, and what role they play in the early stages of infection.
History
DepositionSep 14, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 1, 2023Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: Fiber protein
A: Fiber protein
C: Fiber protein
E: Membrane cofactor protein
D: Desmoglein-2


Theoretical massNumber of molelcules
Total (without water)272,9115
Polymers272,9115
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Fiber protein


Mass: 35564.773 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human adenovirus 11 / Gene: L5 / Production host: Escherichia coli (E. coli) / References: UniProt: P35774
#2: Protein Membrane cofactor protein


Mass: 43795.164 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD46 / Production host: Escherichia coli (E. coli) / References: UniProt: P15529
#3: Protein Desmoglein-2


Mass: 122421.633 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DSG2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q14126
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: Complex between the human adenovirus 11 fiber knob, the human desmoglein 2 (domains ec2/ec3) and the human CD46 (domains SCR1 and SCR2)
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Escherichia coli (E. coli)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 8
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: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 58 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 180510 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0037701
ELECTRON MICROSCOPYf_angle_d0.54110499
ELECTRON MICROSCOPYf_dihedral_angle_d4.6451035
ELECTRON MICROSCOPYf_chiral_restr0.0441201
ELECTRON MICROSCOPYf_plane_restr0.0041361

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