[English] 日本語
Yorodumi
- EMDB-15606: CryoEM structure of the human Nucleophosmin 1 core -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-15606
TitleCryoEM structure of the human Nucleophosmin 1 core
Map data
Sample
  • Complex: Nucleophosmin 1NPM1
    • Protein or peptide: NucleophosminNPM1
Function / homology
Function and homology information


regulation of eIF2 alpha phosphorylation by dsRNA / regulation of mRNA stability involved in cellular response to UV / regulation of endoribonuclease activity / positive regulation of cell cycle G2/M phase transition / negative regulation of centrosome duplication / regulation of endodeoxyribonuclease activity / positive regulation of centrosome duplication / regulation of centriole replication / granular component / positive regulation of protein localization to nucleolus ...regulation of eIF2 alpha phosphorylation by dsRNA / regulation of mRNA stability involved in cellular response to UV / regulation of endoribonuclease activity / positive regulation of cell cycle G2/M phase transition / negative regulation of centrosome duplication / regulation of endodeoxyribonuclease activity / positive regulation of centrosome duplication / regulation of centriole replication / granular component / positive regulation of protein localization to nucleolus / TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation / negative regulation of protein kinase activity by regulation of protein phosphorylation / SARS-CoV-1-host interactions / regulation of centrosome duplication / Tat protein binding / ALK mutants bind TKIs / spindle pole centrosome / cell volume homeostasis / Nuclear import of Rev protein / : / centrosome cycle / regulation of DNA damage response, signal transduction by p53 class mediator / nucleocytoplasmic transport / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / protein kinase inhibitor activity / ribosomal large subunit binding / negative regulation of mRNA splicing, via spliceosome / ribosomal small subunit binding / ribosomal small subunit export from nucleus / Signaling by ALK fusions and activated point mutants / ribosomal large subunit export from nucleus / NF-kappaB binding / Nuclear events stimulated by ALK signaling in cancer / core promoter sequence-specific DNA binding / Deposition of new CENPA-containing nucleosomes at the centromere / ribosomal large subunit biogenesis / ribosome assembly / molecular condensate scaffold activity / positive regulation of translation / SUMOylation of transcription cofactors / positive regulation of protein ubiquitination / regulation of cell growth / protein-DNA complex / intracellular protein transport / PKR-mediated signaling / protein localization / ribosomal small subunit biogenesis / nucleosome assembly / cellular response to UV / cellular senescence / unfolded protein binding / large ribosomal subunit / small ribosomal subunit / positive regulation of NF-kappaB transcription factor activity / histone binding / DNA-binding transcription factor binding / transcription coactivator activity / rRNA binding / protein stabilization / nuclear speck / chromatin remodeling / ribonucleoprotein complex / negative regulation of cell population proliferation / focal adhesion / DNA repair / centrosome / chromatin binding / positive regulation of cell population proliferation / nucleolus / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / nucleoplasm / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function
Nucleophosmin, C-terminal / Nucleophosmin C-terminal domain / Nucleoplasmin core domain / Nucleoplasmin core domain superfamily / Nucleoplasmin/nucleophosmin domain / Nucleoplasmin family
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.53 Å
AuthorsValentin Gese G / Hallberg BM
Funding support Sweden, 1 items
OrganizationGrant numberCountry
Knut and Alice Wallenberg Foundation2017.0080 Sweden
CitationJournal: PNAS Nexus / Year: 2023
Title: A "grappling hook" interaction connects self-assembly and chaperone activity of Nucleophosmin 1.
Authors: Mihkel Saluri / Axel Leppert / Genis Valentin Gese / Cagla Sahin / Dilraj Lama / Margit Kaldmäe / Gefei Chen / Arne Elofsson / Timothy M Allison / Marie Arsenian-Henriksson / Jan Johansson ...Authors: Mihkel Saluri / Axel Leppert / Genis Valentin Gese / Cagla Sahin / Dilraj Lama / Margit Kaldmäe / Gefei Chen / Arne Elofsson / Timothy M Allison / Marie Arsenian-Henriksson / Jan Johansson / David P Lane / B Martin Hällberg / Michael Landreh /
Abstract: How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant ...How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant nucleolar protein that forms large oligomers and undergoes liquid-liquid phase separation by binding RNA or ribosomal proteins. It provides the scaffold for ribosome assembly but also prevents protein aggregation as part of the cellular stress response. Here, we use aggregation assays and native mass spectrometry (MS) to examine the relationship between the self-assembly and chaperone activity of NPM1. We find that oligomerization of full-length NPM1 modulates its ability to retard amyloid formation in vitro. Machine learning-based structure prediction and cryo-electron microscopy reveal fuzzy interactions between the acidic disordered region and the C-terminal nucleotide-binding domain, which cross-link NPM1 pentamers into partially disordered oligomers. The addition of basic peptides results in a tighter association within the oligomers, reducing their capacity to prevent amyloid formation. Together, our findings show that NPM1 uses a "grappling hook" mechanism to form a network-like structure that traps aggregation-prone proteins. Nucleolar proteins and RNAs simultaneously modulate the association strength and chaperone activity, suggesting a mechanism by which nucleolar composition regulates the chaperone activity of NPM1.
History
DepositionAug 18, 2022-
Header (metadata) releaseFeb 15, 2023-
Map releaseFeb 15, 2023-
UpdateFeb 15, 2023-
Current statusFeb 15, 2023Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_15606.png

Downloads & links

-
Map

FileDownload / File: emd_15606.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.51 Å/pix.
x 384 pix.
= 193.92 Å		0.51 Å/pix.
x 384 pix.
= 193.92 Å		0.51 Å/pix.
x 384 pix.
= 193.92 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.505 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0015
Minimum - Maximum-0.0033958023 - 0.0079294825
Average (Standard dev.)1.1540068e-05 (±0.00016223617)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 193.92 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_15606_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #1

Fileemd_15606_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Nucleophosmin 1 class with weaker C-terminal domain density

Fileemd_15606_additional_2.map
AnnotationNucleophosmin 1 class with weaker C-terminal domain density
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Nucleophosmin 1 class with stronger C-terminal domain density

Fileemd_15606_additional_3.map
AnnotationNucleophosmin 1 class with stronger C-terminal domain density
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_15606_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_15606_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Nucleophosmin 1

EntireName: Nucleophosmin 1NPM1
Components
  • Complex: Nucleophosmin 1NPM1
    • Protein or peptide: NucleophosminNPM1

-
Supramolecule #1: Nucleophosmin 1

SupramoleculeName: Nucleophosmin 1 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Nucleophosmin

MacromoleculeName: Nucleophosmin / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 32.708141 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: SMEDSMDMDM SPLRPQNYLF GCELKADKDY HFKVDNDENE HQLSLRTVSL GAGAKDELHI VEAEAMNYEG SPIKVTLATL KMSVQPTVS LGGFEITPPV VLRLKCGSGP VHISGQHLVA VEEDAESEDE EEEDVKLLSI SGKRSAPGGG SKVPQKKVKL A ADEDDDDD ...String:
SMEDSMDMDM SPLRPQNYLF GCELKADKDY HFKVDNDENE HQLSLRTVSL GAGAKDELHI VEAEAMNYEG SPIKVTLATL KMSVQPTVS LGGFEITPPV VLRLKCGSGP VHISGQHLVA VEEDAESEDE EEEDVKLLSI SGKRSAPGGG SKVPQKKVKL A ADEDDDDD DEEDDDEDDD DDDFDDEEAE EKAPVKKSIR DTPAKNAQKS NQNGKDSKPS STPRSKGQES FKKQEKTPKT PK GPSSVED IKAKMQASIE KGGSLPKVEA KFINYVKNCF RMTDQEAIQD LWQWRKSL

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.75 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 54.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 106905
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

5ehd

RefinementSpace: RECIPROCAL / Protocol: FLEXIBLE FIT
Output model

PDB-8as5:
CryoEM structure of the human Nucleophosmin 1 core

+
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