[English] 日本語
Yorodumi
- EMDB-11293: CryoEM Structure of Merkel Cell Polyomavirus Virus-like Particle -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-11293
TitleCryoEM Structure of Merkel Cell Polyomavirus Virus-like Particle
Map data
Sample
  • Virus: Merkel cell polyomavirus
    • Protein or peptide: Capsid protein VP1
Function / homologyCapsid protein VP1,Polyomavirus / Polyomavirus capsid protein VP1 superfamily / Polyomavirus coat protein / Double-stranded DNA virus, group I, capsid / viral capsid / structural molecule activity / Capsid protein VP1
Function and homology information
Biological speciesMerkel cell polyomavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsBayer NJ / Januliene D / Stehle T / Moeller A / Blaum BS
Funding support Germany, 3 items
OrganizationGrant numberCountry
German Research Foundation (DFG)BL1294/3-1 Germany
German Research Foundation (DFG)STE 1463/7-1 Germany
German Research Foundation (DFG)FOR 2327 ViroCarb 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 7, 2020-
Current statusOct 7, 2020Processing site: PDBe / Status: Released

-
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
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_11293.png

Downloads & links

-
Map

FileDownload / File: emd_11293.map.gz / Format: CCP4 / Size: 561.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.053 Å
Density
Contour LevelBy AUTHOR: 6.96 / Movie #1: 9.96
Minimum - Maximum-32.2356 - 43.813934
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

-
Supplemental data

-
Additional map: Merkel Cell polyomavirus (unsharpened map).

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

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_11293_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_11293_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Merkel cell polyomavirus

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

-
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)
Host systemOrganism: Homo sapiens (human) / Recombinant cell: HEK293TT / Recombinant plasmid: pwM
Virus shellShell ID: 1 / Diameter: 508.0 Å / T number (triangulation number): 7

-
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

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1 mg/mL
BufferpH: 6.6
Component:
ConcentrationFormulaName
20.0 mMC8H18N2O4SHEPES
150.0 mMNaClSodium chloridesodium 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

-
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: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 75000
Sample stageCooling holder cryogen: NITROGEN
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
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Particle selectionNumber selected: 23349
CTF correctionSoftware - Name: CTFFIND (ver. 4)
Details: CTF correction was performed within 3D reconstruction
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: FREALIGN
Final 3D classificationNumber classes: 3 / Software - Name: cisTEM
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cisTEM
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
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial model
PDB IDChain

6zlz

chain_id: A

6zlz

chain_id: B

6zlz

chain_id: C

6zlz

chain_id: D

6zlz

chain_id: E

6zlz

chain_id: F
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

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more