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- EMDB-18455: Human Adenovirus type 11 fiber knob in complex with its cell rece... -

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Basic information

Entry
Database: EMDB / ID: EMD-18455
TitleHuman Adenovirus type 11 fiber knob in complex with its cell receptors, Desmoglein-2 and CD46
Map dataThis is the 3D reconstruction of hAd11k in complex with rDSG2 and CD46
Sample
  • Complex: Complex between the human adenovirus 11 fiber knob, the human desmoglein 2 (domains ec2/ec3) and the human CD46 (domains SCR1 and SCR2)
    • Protein or peptide: Fiber proteinFibrous protein
    • Protein or peptide: Membrane cofactor proteinCD46
    • Protein or peptide: Desmoglein-2
Keywordsadenovirus / cell entry / receptor binding / VIRAL PROTEIN
Function / homology
Function and homology information


sequestering of extracellular ligand from receptor / inner acrosomal membrane / Purkinje myocyte development / bundle of His cell-Purkinje myocyte adhesion involved in cell communication / cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication / negative regulation of complement activation, classical pathway / desmosome organization / Keratinization / T cell mediated immunity / desmosome ...sequestering of extracellular ligand from receptor / inner acrosomal membrane / Purkinje myocyte development / bundle of His cell-Purkinje myocyte adhesion involved in cell communication / cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication / negative regulation of complement activation, classical pathway / desmosome organization / Keratinization / T cell mediated immunity / desmosome / regulation of Notch signaling pathway / positive regulation of transforming growth factor beta production / Formation of the cornified envelope / cornified envelope / positive regulation of memory T cell differentiation / regulation of ventricular cardiac muscle cell action potential / positive regulation of regulatory T cell differentiation / Apoptotic cleavage of cell adhesion proteins / adhesion receptor-mediated virion attachment to host cell / homophilic cell adhesion via plasma membrane adhesion molecules / single fertilization / regulation of heart rate by cardiac conduction / positive regulation of interleukin-10 production / RHOG GTPase cycle / intercalated disc / maternal process involved in female pregnancy / lateral plasma membrane / RAC2 GTPase cycle / RAC3 GTPase cycle / complement activation, classical pathway / positive regulation of T cell proliferation / cell adhesion molecule binding / response to progesterone / Regulation of Complement cascade / cell-cell adhesion / viral capsid / cell-cell junction / virus receptor activity / signaling receptor activity / cell junction / adaptive immune response / cell adhesion / cadherin binding / symbiont entry into host cell / apical plasma membrane / negative regulation of gene expression / focal adhesion / intracellular membrane-bounded organelle / innate immune response / host cell nucleus / calcium ion binding / positive regulation of gene expression / cell surface / extracellular space / extracellular exosome / plasma membrane
Similarity search - Function
Membrane cofactor protein CD46 / Desmosomal cadherin / Adenoviral fibre protein, knob / Adenoviral fibre protein (knob domain) / Adenoviral fibre protein, repeat/shaft region / Adenoviral fibre protein (repeat/shaft region) / Adenovirus fibre protein / Catenin binding domain superfamily / Attachment protein shaft domain superfamily / Adenovirus pIV-like, attachment domain ...Membrane cofactor protein CD46 / Desmosomal cadherin / Adenoviral fibre protein, knob / Adenoviral fibre protein (knob domain) / Adenoviral fibre protein, repeat/shaft region / 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 / Cadherins domain profile. / Cadherin-like / 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 speciesEscherichia coli (E. coli) / Human adenovirus 11 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsEffantin G
Funding support France, 1 items
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, 2023-
Header (metadata) releaseNov 1, 2023-
Map releaseNov 1, 2023-
UpdateDec 13, 2023-
Current statusDec 13, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_18455.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThis is the 3D reconstruction of hAd11k in complex with rDSG2 and CD46
Voxel sizeX=Y=Z: 0.84 Å
Density
Contour LevelBy AUTHOR: 0.009
Minimum - Maximum-0.018136717 - 0.0424414
Average (Standard dev.)0.00006339459 (±0.0015430214)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions250250250
Spacing250250250
CellA=B=C: 210.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_18455_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: This is the 3D reconstruction of hAd11k in...

Fileemd_18455_half_map_1.map
AnnotationThis is the 3D reconstruction of hAd11k in complex with rDSG2 and CD46 - half map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: This is the 3D reconstruction of hAd11k in...

Fileemd_18455_half_map_2.map
AnnotationThis is the 3D reconstruction of hAd11k in complex with rDSG2 and CD46 - half map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Complex between the human adenovirus 11 fiber knob, the human des...

EntireName: Complex between the human adenovirus 11 fiber knob, the human desmoglein 2 (domains ec2/ec3) and the human CD46 (domains SCR1 and SCR2)
Components
  • Complex: Complex between the human adenovirus 11 fiber knob, the human desmoglein 2 (domains ec2/ec3) and the human CD46 (domains SCR1 and SCR2)
    • Protein or peptide: Fiber proteinFibrous protein
    • Protein or peptide: Membrane cofactor proteinCD46
    • Protein or peptide: Desmoglein-2

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Supramolecule #1: Complex between the human adenovirus 11 fiber knob, the human des...

SupramoleculeName: 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 / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Escherichia coli (E. coli)

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Macromolecule #1: Fiber protein

MacromoleculeName: Fiber protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human adenovirus 11
Molecular weightTheoretical: 35.564773 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MTKRVRLSDS FNPVYPYEDE STSQHPFINP GFISPNGFTQ SPNGVLTLKC LTPLTTTGGS LQLKVGGGLT VDDTNGFLKE NISATTPLV KTGHSIGLPL GAGLGTNENK LCIKLGQGLT FNSNNICIDD NINTLWTGVN PTEANCQIMN SSESNDCKLI L TLVKTGAL ...String:
MTKRVRLSDS FNPVYPYEDE STSQHPFINP GFISPNGFTQ SPNGVLTLKC LTPLTTTGGS LQLKVGGGLT VDDTNGFLKE NISATTPLV KTGHSIGLPL GAGLGTNENK LCIKLGQGLT FNSNNICIDD NINTLWTGVN PTEANCQIMN SSESNDCKLI L TLVKTGAL VTAFVYVIGV SNNFNMLTTH RNINFTAELF FDSTGNLLTR LSSLKTPLNH KSGQNMATGA ITNAKGFMPS TT AYPFNDN SREKENYIYG TCYYTASDRT AFPIDISVML NRRAINDETS YCIRITWSWN TGDAPEVQTS ATTLVTSPFT FYY IREDD

UniProtKB: Fiber protein

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Macromolecule #2: Membrane cofactor protein

MacromoleculeName: Membrane cofactor protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.795164 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MEPPGRRECP FPSWRFPGLL LAAMVLLLYS FSDACEEPPT FEAMELIGKP KPYYEIGERV DYKCKKGYFY IPPLATHTIC DRNHTWLPV SDDACYRETC PYIRDPLNGQ AVPANGTYEF GYQMHFICNE GYYLIGEEIL YCELKGSVAI WSGKPPICEK V LCTPPPKI ...String:
MEPPGRRECP FPSWRFPGLL LAAMVLLLYS FSDACEEPPT FEAMELIGKP KPYYEIGERV DYKCKKGYFY IPPLATHTIC DRNHTWLPV SDDACYRETC PYIRDPLNGQ AVPANGTYEF GYQMHFICNE GYYLIGEEIL YCELKGSVAI WSGKPPICEK V LCTPPPKI KNGKHTFSEV EVFEYLDAVT YSCDPAPGPD PFSLIGESTI YCGDNSVWSR AAPECKVVKC RFPVVENGKQ IS GFGKKFY YKATVMFECD KGFYLDGSDT IVCDSNSTWD PPVPKCLKVL PPSSTKPPAL SHSVSTSSTT KSPASSASGP RPT YKPPVS NYPGYPKPEE GILDSLDVWV IAVIVIAIVV GVAVICVVPY RYLQRRKKKG TYLTDETHRE VKFTSL

UniProtKB: Membrane cofactor protein

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Macromolecule #3: Desmoglein-2

MacromoleculeName: Desmoglein-2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 122.421633 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MARSPGRAYA LLLLLICFNV GSGLHLQVLS TRNENKLLPK HPHLVRQKRA WITAPVALRE GEDLSKKNPI AKIHSDLAEE RGLKITYKY TGKGITEPPF GIFVFNKDTG ELNVTSILDR EETPFFLLTG YALDARGNNV EKPLELRIKV LDINDNEPVF T QDVFVGSV ...String:
MARSPGRAYA LLLLLICFNV GSGLHLQVLS TRNENKLLPK HPHLVRQKRA WITAPVALRE GEDLSKKNPI AKIHSDLAEE RGLKITYKY TGKGITEPPF GIFVFNKDTG ELNVTSILDR EETPFFLLTG YALDARGNNV EKPLELRIKV LDINDNEPVF T QDVFVGSV EELSAAHTLV MKINATDADE PNTLNSKISY RIVSLEPAYP PVFYLNKDTG EIYTTSVTLD REEHSSYTLT VE ARDGNGE VTDKPVKQAQ VQIRILDVND NIPVVENKVL EGMVEENQVN VEVTRIKVFD ADEIGSDNWL ANFTFASGNE GGY FHIETD AQTNEGIVTL IKEVDYEEMK NLDFSVIVAN KAAFHKSIRS KYKPTPIPIK VKVKNVKEGI HFKSSVISIY VSES MDRSS KGQIIGNFQA FDEDTGLPAH ARYVKLEDRD NWISVDSVTS EIKLAKLPDF ESRYVQNGTY TVKIVAISED YPRKT ITGT VLINVEDIND NCPTLIEPVQ TICHDAEYVN VTAEDLDGHP NSGPFSFSVI DKPPGMAEKW KIARQESTSV LLQQSE KKL GRSEIQFLIS DNQGFSCPEK QVLTLTVCEC LHGSGCREAQ HDSYVGLGPA AIALMILAFL LLLLVPLLLL MCHCGKG AK GFTPIPGTIE MLHPWNNEGA PPEDKVVPSF LPVDQGGSLV GRNGVGGMAK EATMKGSSSA SIVKGQHEMS EMDGRWEE H RSLLSGRATQ FTGATGAIMT TETTKTARAT GASRDMAGAQ AAAVALNEEF LRNYFTDKAA SYTEEDENHT AKDCLLVYS QEETESLNAS IGCCSFIEGE LDDRFLDDLG LKFKTLAEVC LGQKIDINKE IEQRQKPATE TSMNTASHSL CEQTMVNSEN TYSSGSSFP VPKSLQEANA EKVTQEIVTE RSVSSRQAQK VATPLPDPMA SRNVIATETS YVTGSTMPPT TVILGPSQPQ S LIVTERVY APASTLVDQP YANEGTVVVT ERVIQPHGGG SNPLEGTQHL QDVPYVMVRE RESFLAPSSG VQPTLAMPNI AV GQNVTVT ERVLAPASTL QSSYQIPTEN SMTARNTTVS GAGVPGPLPD FGLEESGHSN STITTSSTRV TKHSTVQHSY S

UniProtKB: Desmoglein-2

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 58.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Initial angle assignmentType: OTHER
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 180510
FSC plot (resolution estimation)

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