[English] 日本語
Yorodumi
- PDB-6zlz: Crystal Structure of Merkel Cell Polyomavirus Virus-like Particle -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6zlz
TitleCrystal Structure of Merkel Cell Polyomavirus Virus-like Particle
ComponentsCapsid protein VP1
KeywordsVIRUS LIKE PARTICLE / polyomavirus / capsid / Merkel cell carcinoma / jelly roll fold
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
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.52 Å
AuthorsBayer, N.J. / Stehle, T. / Blaum, B.S.
Funding support Germany, 3items
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 1, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 5, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 7, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Jan 31, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Capsid protein VP1
B: Capsid protein VP1
C: Capsid protein VP1
D: Capsid protein VP1
E: Capsid protein VP1
F: Capsid protein VP1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)279,90712
Polymers279,6666
Non-polymers2406
Water0
1
A: Capsid protein VP1
B: Capsid protein VP1
C: Capsid protein VP1
D: Capsid protein VP1
E: Capsid protein VP1
F: Capsid protein VP1
hetero molecules
x 60


Theoretical massNumber of molelcules
Total (without water)16,794,399720
Polymers16,779,971360
Non-polymers14,428360
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
point symmetry operation59
Unit cell
Length a, b, c (Å)554.830, 560.990, 573.660
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number23
Space group name H-MI222
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2generate(-0.301755, -0.493644, -0.815634), (0.497208, -0.811442, 0.307158), (-0.813466, -0.312854, 0.490301)501.767365, 369.959869, 314.206268
3generate(-0.305971, 0.505448, -0.806786), (-0.496729, -0.807694, -0.317634), (-0.812184, 0.303567, 0.498201)220.679947, 646.352295, 139.640625
4generate(0.50031, 0.813848, -0.295537), (-0.804734, 0.311112, -0.505581), (-0.319521, 0.490776, 0.810583)-91.773033, 417.881561, -51.007481
5generate(0.502433, -0.806165, -0.312505), (0.807048, 0.307595, 0.504043), (-0.310217, -0.505454, 0.80516)365.167725, -30.624809, 228.217804
6generate(0.803476, 0.308132, 0.509392), (0.312774, 0.509555, -0.801577), (-0.506555, 0.803373, 0.31304)-34.047642, 50.277401, -86.532898
7generate(-0.500191, -0.809063, -0.308587), (0.80893, -0.30945, -0.499874), (0.308938, -0.499657, 0.809259)643.100586, 142.951202, 54.338261
8generate(-0.807549, 0.3111, -0.501081), (0.313299, -0.493538, -0.811335), (-0.499709, -0.81218, 0.301089)414.6633, 333.25354, 367.517456
9generate(-0.00324, 0.999968, 0.007371), (0.004701, 0.007386, -0.999962), (-0.999984, -0.003205, -0.004724)-3.59973, 278.010345, 278.684418
10generate(0.498621, -0.810187, 0.30818), (0.813454, 0.314531, -0.489247), (0.299449, 0.494639, 0.815882)366.40625, -34.450939, -224.365295
11generate(0.818132, -0.316485, -0.480101), (-0.279732, 0.510419, -0.813156), (0.502404, 0.799569, 0.329059)137.132248, 219.782166, -366.476196
12generate(0.312346, -0.489451, -0.814173), (0.493118, 0.816077, -0.301418), (0.811957, -0.307336, 0.496256)329.720337, -86.944588, -137.682907
13generate(0.304564, 0.511267, -0.803646), (0.50659, -0.801447, -0.317882), (-0.806602, -0.310304, -0.503095)48.4217, 367.539215, 311.430969
14generate(0.810809, 0.317576, -0.491665), (-0.302105, -0.492401, -0.816256), (-0.50132, 0.810362, -0.303302)-37.703659, 504.703888, -89.340057
15generate(0.027895, 0.008488, -0.999575), (0.999522, -0.013573, 0.027778), (-0.013331, -0.999872, -0.008863)271.181152, 2.62097, 283.754944

-
Components

#1: Protein
Capsid protein VP1 / / VP1


Mass: 46611.031 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Merkel cell polyomavirus / Gene: VP1 / Plasmid: pwM / Cell line (production host): HEK293TT / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: B0G0W3
#2: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

Crystal
ID
2
1
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 4.6
Details: 0.1 M sodium citrate, 0.2 M sodium chloride, 30% MPD

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 25, 2016
RadiationMonochromator: M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 3.52→50 Å / Num. obs: 1088665 / % possible obs: 99.8 % / Redundancy: 13.5 % / Biso Wilson estimate: 97.6 Å2 / CC1/2: 0.996 / Rrim(I) all: 0.309 / Net I/σ(I): 9.15
Reflection shellResolution: 3.52→3.6 Å / Redundancy: 12.6 % / Mean I/σ(I) obs: 1.06 / Num. unique obs: 78618 / CC1/2: 0.332 / Rrim(I) all: 2.883 / % possible all: 98.3

-
Processing

Software
NameVersionClassification
PHENIX1.13refinement
PDB_EXTRACT3.25data extraction
XDS20151231data reduction
XDS20151231data scaling
PHASER2.6.0phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1sva

1sva


Resolution: 3.52→49.97 Å / Cross valid method: NONE
Details: NCS-constraint refinement procedure with NCS map averaging
RfactorNum. reflection% reflection
Rwork0.235 --
obs-1088487 99.86 %
Displacement parametersBiso max: 190.55 Å2 / Biso mean: 122.6 Å2 / Biso min: 88.69 Å2
Refinement stepCycle: LAST / Resolution: 3.52→49.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms16318 0 6 0 16324

+
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