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- EMDB-11293: CryoEM Structure of Merkel Cell Polyomavirus -

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Basic information

Entry
Database: EMDB / ID: EMD-11293
TitleCryoEM Structure of Merkel Cell Polyomavirus
Map data
Sample
  • Virus: Merkel cell polyomavirus
    • Protein or peptide: Capsid protein VP1
Keywordspolyomavirus / capsid / Merkel cell carcinoma / jelly roll fold / VIRUS LIKE PARTICLE
Function / homologyCapsid protein VP1,Polyomavirus / Polyomavirus capsid protein VP1 superfamily / Polyomavirus coat protein / Double-stranded DNA virus, group I, capsid / viral capsid / host cell nucleus / structural molecule activity / metal ion binding / VP1
Function and homology information
Biological speciesMerkel cell polyomavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsBayer NJ / Januliene D
Funding support Germany, 3 items
OrganizationGrant numberCountry
German Research Foundation (DFG)BL1294/3-1 Germany
German Research Foundation (DFG)FOR 2327 ViroCarb Germany
German Research Foundation (DFG)STE 1463/7-1 Germany
CitationJournal: J Virol / Year: 2020
Title: Structure of Merkel Cell Polyomavirus Capsid and Interaction with Its Glycosaminoglycan Attachment Receptor.
Authors: Niklas J Bayer / Dovile Januliene / Georg Zocher / Thilo Stehle / Arne Moeller / Bärbel S Blaum /
Abstract: Merkel cell polyomavirus (MCPyV) is a human double-stranded DNA tumor virus. MCPyV cell entry is unique among members of the polyomavirus family as it requires the engagement of two types of glycans, ...Merkel cell polyomavirus (MCPyV) is a human double-stranded DNA tumor virus. MCPyV cell entry is unique among members of the polyomavirus family as it requires the engagement of two types of glycans, sialylated oligosaccharides and sulfated glycosaminoglycans (GAGs). Here, we present crystallographic and cryo-electron microscopic structures of the icosahedral MCPyV capsid and analysis of its glycan interactions via nuclear magnetic resonance (NMR) spectroscopy. While sialic acid binding is specific for α2-3-linked sialic acid and mediated by the exposed apical loops of the major capsid protein VP1, a broad range of GAG oligosaccharides bind to recessed regions between VP1 capsomers. Individual VP1 capsomers are tethered to one another by an extensive disulfide network that differs in architecture from previously described interactions for other PyVs. An unusual C-terminal extension in MCPyV VP1 projects from the recessed capsid regions. Mutagenesis experiments show that this extension is dispensable for receptor interactions. The MCPyV genome was found to be clonally integrated in 80% of cases of Merkel cell carcinoma (MCC), a rare but aggressive form of human skin cancer, strongly suggesting that this virus is tumorigenic. In the metastasizing state, the course of the disease is often fatal, especially in immunocompromised individuals, as reflected by the high mortality rate of 33 to 46% and the low 5-year survival rate (<45%). The high seroprevalence of about 60% makes MCPyV a serious health care burden and illustrates the need for targeted treatments. In this study, we present the first high-resolution structural data for this human tumor virus and demonstrate that the full capsid is required for the essential interaction with its GAG receptor(s). Together, these data can be used as a basis for future strategies in drug development.
History
DepositionJul 3, 2020-
Header (metadata) releaseAug 5, 2020-
Map releaseAug 5, 2020-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 9.96
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 9.96
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6zml
  • Surface level: 9.96
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6zml
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_11293.png

Downloads & links

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Map

FileDownload / File: emd_11293.map.gz / Format: CCP4 / Size: 561.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.05 Å/pix.
x 528 pix.
= 555.984 Å		1.05 Å/pix.
x 528 pix.
= 555.984 Å		1.05 Å/pix.
x 528 pix.
= 555.984 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.053 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 6.96 / Movie #1: 9.96
Minimum - Maximum-32.235599999999998 - 43.813934000000003
Average (Standard dev.)0.08941572 (±3.4765656)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions528528528
Spacing528528528
CellA=B=C: 555.984 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0531.0531.053
M x/y/z528528528
origin x/y/z0.0000.0000.000
length x/y/z555.984555.984555.984
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS528528528
D min/max/mean-32.23643.8140.089

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Supplemental data

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Additional map: Merkel Cell polyomavirus (unsharpened map).

Fileemd_11293_additional.map
AnnotationMerkel Cell polyomavirus (unsharpened map).
Projections & Slices
AxesZYX

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Histogram (log scale)

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Half map: #1

Fileemd_11293_half_map_1.map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_11293_half_map_2.map
Projections & Slices
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Sample components

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Entire : Merkel cell polyomavirus

EntireName: Merkel cell polyomavirus
Components
  • Virus: Merkel cell polyomavirus
    • Protein or peptide: Capsid protein VP1

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Supramolecule #1: Merkel cell polyomavirus

SupramoleculeName: Merkel cell polyomavirus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 493803 / Sci species name: Merkel cell polyomavirus / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: OTHER / Virus enveloped: No / Virus empty: Yes
Host (natural)Organism: Homo sapiens (human)
Virus shellShell ID: 1 / Diameter: 508.0 Å / T number (triangulation number): 7

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Macromolecule #1: Capsid protein VP1

MacromoleculeName: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Merkel cell polyomavirus
Molecular weightTheoretical: 46.611031 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAPKRKASST CKTPKRQCIP KPGCCPNVAS VPKLLVKGGV EVLSVVTGED SITQIELYLN PRMGVNSPDL PTTSNWYTYT YDLQPKGSS PDQPIKENLP AYSVARVSLP MLNEDITCDT LQMWEAISVK TEVVGISSLI NVHYWDMKRV HDYGAGIPVS G VNYHMFAI ...String:
MAPKRKASST CKTPKRQCIP KPGCCPNVAS VPKLLVKGGV EVLSVVTGED SITQIELYLN PRMGVNSPDL PTTSNWYTYT YDLQPKGSS PDQPIKENLP AYSVARVSLP MLNEDITCDT LQMWEAISVK TEVVGISSLI NVHYWDMKRV HDYGAGIPVS G VNYHMFAI GGEPLDLQGL VLDYQTQYPK TTNGGPITIE TVLGRKMTPK NQGLDPQAKA KLDKDGNYPI EVWCPDPSKN EN SRYYGSI QTGSQTPTVL QFSNTLTTVL LDENGVGPLC KGDGLFISCA DIVGFLFKTS GKMALHGLPR YFNVTLRKRW VKN PYPVVN LINSLFSNLM PKVSGQPMEG KDNQVEEVRI YEGSEQLPGD PDIVRFLDKF GQEKTVYPKP SVAPAAVTFQ SNQQ DKGKA PLKGPQKASQ KESQTQEL

UniProtKB: VP1

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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

Concentration1 mg/mL
BufferpH: 6.6
Component:
ConcentrationFormulaName
20.0 mMC8H18N2O4SHEPES
150.0 mMNaClsodium chloride
1.0 mMCaCl2calcium chloride

Details: Solution was sterile filtered
GridModel: C-flat-2/2 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 463 / Average exposure time: 67.0 sec. / Average electron dose: 30.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 75000
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 23349
Startup modelType of model: NONE
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 22310
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: FREALIGN
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cisTEM
Final 3D classificationNumber classes: 3 / Software - Name: cisTEM
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChain

6zlz

chain_id: A, source_name: PDB, initial_model_type: experimental model

6zlz

chain_id: B, source_name: PDB, initial_model_type: experimental model

6zlz

chain_id: C, source_name: PDB, initial_model_type: experimental model

6zlz

chain_id: D, source_name: PDB, initial_model_type: experimental model

6zlz

chain_id: E, source_name: PDB, initial_model_type: experimental model

6zlz

chain_id: F, source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT / Overall B value: 105.92 / Target criteria: Correlation coefficient
Output model

PDB-6zml:
CryoEM Structure of Merkel Cell Polyomavirus Virus-like Particle

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