[English] 日本語
Yorodumi
- EMDB-42595: Structure of the Measles virus Fusion protein in the pre-fusion c... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-42595
TitleStructure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
Map datamap sharp
Sample
  • Complex: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
    • Protein or peptide: Fusion glycoprotein F0
    • Protein or peptide: Fusion glycoprotein F0
    • Protein or peptide: [FIP-HRC]2-PEG11
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water
KeywordsVIRAL PROTEIN / glycoprotein / immune system / measles / high-resolution / ectodomain / post-fusion / small molecule / inhibitor / complex
Function / homologyPrecursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane / Fusion glycoprotein F0
Function and homology information
Biological speciesMeasles virus strain Ichinose-B95a / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.34 Å
AuthorsZyla D / Saphire EO
Funding support Switzerland, United States, 5 items
OrganizationGrant numberCountry
Swiss National Science FoundationP2EZP3_195680 Switzerland
Swiss National Science FoundationP500PB_210992 Switzerland
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS105699 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS091263 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI176833 United States
CitationJournal: Science / Year: 2024
Title: A neutralizing antibody prevents postfusion transition of measles virus fusion protein.
Authors: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben ...Authors: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben Parekh / Tara C Marcink / Ruben Diaz Avalos / Branka Horvat / Cyrille Mathieu / Joost Snijder / Alexander L Greninger / Kathryn M Hastie / Stefan Niewiesk / Anne Moscona / Matteo Porotto / Erica Ollmann Saphire /
Abstract: Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be ...Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.
History
DepositionNov 1, 2023-
Header (metadata) releaseJul 3, 2024-
Map releaseJul 3, 2024-
UpdateJul 24, 2024-
Current statusJul 24, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_42595.png

Downloads & links

-
Map

FileDownload / File: emd_42595.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmap sharp
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.88 Å/pix.
x 300 pix.
= 264. Å		0.88 Å/pix.
x 300 pix.
= 264. Å		0.88 Å/pix.
x 300 pix.
= 264. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.88 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.401
Minimum - Maximum-2.731061 - 4.5829377
Average (Standard dev.)-0.00010952017 (±0.14013836)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 264.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_42595_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half 1

Fileemd_42595_half_map_1.map
Annotationhalf 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half 2

Fileemd_42595_half_map_2.map
Annotationhalf 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Structure of the Measles virus Fusion protein in the pre-fusion c...

EntireName: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
Components
  • Complex: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
    • Protein or peptide: Fusion glycoprotein F0
    • Protein or peptide: Fusion glycoprotein F0
    • Protein or peptide: [FIP-HRC]2-PEG11
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water

-
Supramolecule #1: Structure of the Measles virus Fusion protein in the pre-fusion c...

SupramoleculeName: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Measles virus strain Ichinose-B95a / Strain: Ichinose-B95a

-
Macromolecule #1: Fusion glycoprotein F0

MacromoleculeName: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Measles virus strain Ichinose-B95a
Molecular weightTheoretical: 12.498768 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString:
MGLKVNVSAI FMAVLLTLQT PTGQIHWGNL SKIGVVGIGS ASYKVMTRSS HQSLVIKLMP NITLLNNCTR VEIAEYRRLL RTVLEPIRD ALNAMTQNIR PVQSVASSRR HKR

UniProtKB: Fusion glycoprotein F0

-
Macromolecule #2: Fusion glycoprotein F0

MacromoleculeName: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Measles virus strain Ichinose-B95a
Molecular weightTheoretical: 44.89882 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: FAGVVLAGAA LGVATAAQIT AGIALHQSML NSQAIDNLRA SLETTNQAIE AIRQAGQGMI LAVQGVQDYI NNELIPSMNQ LSCDLIGQK LGLKLLRYYT EILSLFGPSL RDPISAEISI QALSYALGGD INKVLEKLGY SGGDLLGILE SRGIKARITH V DTESYFIV ...String:
FAGVVLAGAA LGVATAAQIT AGIALHQSML NSQAIDNLRA SLETTNQAIE AIRQAGQGMI LAVQGVQDYI NNELIPSMNQ LSCDLIGQK LGLKLLRYYT EILSLFGPSL RDPISAEISI QALSYALGGD INKVLEKLGY SGGDLLGILE SRGIKARITH V DTESYFIV LSIAYPTLSE IKGVIVHRLE GVSYNIGSQE WYTTVPKYVA TQGYLISNFD ESSCTFMPEG TVCSQNALYP MS PLLQECL RGSTKSCART LVSGSFGNRF ILSQGNLIAN CASILCKCYT TGTIINQDPD KILTYIAADH CPVVEVNGVT IQV GSRRYP DAVYLHRIDL GPPISLGRLD VGTNLGNAIA KLEDAKELLE SSDQILRSMK GLSSTSIGVD DDDKAGWSHP QFEK GGGSG GGSGGGSWSH PQFEK

UniProtKB: Fusion glycoprotein F0

-
Macromolecule #3: [FIP-HRC]2-PEG11

MacromoleculeName: [FIP-HRC]2-PEG11 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 503.546 Da
SequenceString:
(P6S)FFG

-
Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #7: water

MacromoleculeName: water / type: ligand / ID: 7 / Number of copies: 33 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.38 mg/mL
BufferpH: 8 / Details: HEPES 50 mM, pH 8.0, NaCl 150 mM
GridModel: Quantifoil R2/2 / Material: COPPER / Mesh: 400 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 3 / Number real images: 10716 / Average exposure time: 2.0 sec. / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 3000000
Startup modelType of model: INSILICO MODEL
Final reconstructionNumber classes used: 1 / Resolution.type: BY AUTHOR / Resolution: 2.34 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.2) / Number images used: 235000
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software: (Name: cryoSPARC, RELION)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationNumber classes: 3 / Software - Name: RELION

-
Atomic model buiding 1

Initial modelPDB ID:

5yxw


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-8uuq:
Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11

+
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