[English] 日本語
Yorodumi
- PDB-8duw: HnRNPA2 D290V LCD PM2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8duw
TitleHnRNPA2 D290V LCD PM2
ComponentsHeterogeneous nuclear ribonucleoproteins A2/B1
KeywordsPROTEIN FIBRIL / Amyloid
Function / homology
Function and homology information


positive regulation of telomerase RNA reverse transcriptase activity / miRNA transport / RNA transport / positive regulation of telomere maintenance via telomere lengthening / G-quadruplex DNA unwinding / primary miRNA processing / G-rich strand telomeric DNA binding / single-stranded telomeric DNA binding / N6-methyladenosine-containing RNA reader activity / miRNA binding ...positive regulation of telomerase RNA reverse transcriptase activity / miRNA transport / RNA transport / positive regulation of telomere maintenance via telomere lengthening / G-quadruplex DNA unwinding / primary miRNA processing / G-rich strand telomeric DNA binding / single-stranded telomeric DNA binding / N6-methyladenosine-containing RNA reader activity / miRNA binding / negative regulation of mRNA splicing, via spliceosome / Processing of Capped Intron-Containing Pre-mRNA / mRNA transport / Cajal body / mRNA export from nucleus / pre-mRNA intronic binding / catalytic step 2 spliceosome / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / molecular condensate scaffold activity / mRNA Splicing - Major Pathway / mRNA 3'-UTR binding / spliceosomal complex / mRNA splicing, via spliceosome / mRNA processing / nuclear matrix / chromosome, telomeric region / ribonucleoprotein complex / negative regulation of transcription by RNA polymerase II / RNA binding / extracellular exosome / nucleoplasm / membrane / identical protein binding / nucleus / cytoplasm
Similarity search - Function
hnRNP A2/B1, RNA recognition motif 1 / Heterogeneous nuclear ribonucleoprotein A1/A2, C-terminal / Heterogeneous nuclear ribonucleoprotein A1, LC domain / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Nucleotide-binding alpha-beta plait domain superfamily
Similarity search - Domain/homology
Heterogeneous nuclear ribonucleoproteins A2/B1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsEisenberg, D.S. / Lu, J. / Ge, P. / Boyer, D.R.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Aging (NIH/NIA)AG070895 United States
National Institutes of Health/National Institute on Aging (NIH/NIA)AG048120 United States
CitationJournal: J Biol Chem / Year: 2024
Title: Cryo-EM structures of the D290V mutant of the hnRNPA2 low-complexity domain suggests how D290V affects phase separation and aggregation.
Authors: Jiahui Lu / Peng Ge / Michael R Sawaya / Michael P Hughes / David R Boyer / Qin Cao / Romany Abskharon / Duilio Cascio / Einav Tayeb-Fligelman / David S Eisenberg /
Abstract: Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, ...Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in multisystem proteinopathy known to afflict two families, mainly with myopathy and Paget's disease of bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain. We find that the mutant form of hnRNPA2 differs from the WT fibrils in four ways. In contrast to the WT fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones. Also, the mutant fibrils are more stable than WT fibrils as judged by phase separation, thermal stability, and energetic calculations. Similar to other pathogenic amyloids, the mutant fibrils are polymorphic. Thus, these structures offer evidence to explain how a D-to-V missense mutation diverts the assembly of reversible, functional amyloid-like fibrils into the assembly of pathogenic amyloid, and may shed light on analogous conversions occurring in other ribonucleoproteins that lead to neurological diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.
History
DepositionJul 27, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 2, 2023Provider: repository / Type: Initial release
Revision 1.1Dec 20, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Feb 14, 2024Group: Database references / Category: citation / Item: _citation.journal_volume

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Heterogeneous nuclear ribonucleoproteins A2/B1
B: Heterogeneous nuclear ribonucleoproteins A2/B1
C: Heterogeneous nuclear ribonucleoproteins A2/B1
D: Heterogeneous nuclear ribonucleoproteins A2/B1
E: Heterogeneous nuclear ribonucleoproteins A2/B1
F: Heterogeneous nuclear ribonucleoproteins A2/B1
G: Heterogeneous nuclear ribonucleoproteins A2/B1
H: Heterogeneous nuclear ribonucleoproteins A2/B1
I: Heterogeneous nuclear ribonucleoproteins A2/B1
J: Heterogeneous nuclear ribonucleoproteins A2/B1


Theoretical massNumber of molelcules
Total (without water)153,91810
Polymers153,91810
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1chain "A"
d_2ens_1chain "B"
d_3ens_1chain "C"
d_4ens_1chain "D"
d_5ens_1chain "E"
d_6ens_1chain "F"
d_7ens_1chain "G"
d_8ens_1chain "H"
d_9ens_1chain "I"
d_10ens_1chain "J"

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg label comp-IDEnd label comp-IDLabel asym-IDLabel seq-ID
d_11ens_1GLYGLYA263 - 316
d_21ens_1GLYGLYB263 - 316
d_31ens_1GLYGLYC263 - 316
d_41ens_1GLYGLYD263 - 316
d_51ens_1GLYGLYE263 - 316
d_61ens_1GLYGLYF263 - 316
d_71ens_1GLYGLYG263 - 316
d_81ens_1GLYGLYH263 - 316
d_91ens_1GLYGLYI263 - 316
d_101ens_1GLYGLYJ263 - 316

NCS oper:
IDCodeMatrixVector
1given(-0.999966274368, -0.00818405020954, 0.000686620596379), (0.00818494172603, -0.999965650207, 0.001305807884), (0.000675910213817, 0.00131138379438, 0.999998911708)138.518572879, 137.328959214, 2.2154682797
2given(-0.999988796211, 0.00463043400827, -0.000983124502689), (-0.00463051203941, -0.999989276149, 7.71092070582E-5), (-0.000982756910713, 8.16607129889E-5, 0.99999951376)137.747863638, 138.287738855, -2.325893333
3given(0.999877563754, 0.0155987995897, 0.00123893192461), (-0.0155983172668, 0.999878259629, -0.000398019152594), (-0.00124498971757, 0.000378645167391, 0.999999153314)-1.15844608308, 1.10694678979, 4.8470576896
4given(0.999931776639, -0.0116651054791, 0.000606119899885), (0.0116652301352, 0.999931938376, -0.00020253559504), (-0.000603716047301, 0.000209592305503, 0.999999795799)0.748569356312, -0.763941811495, -4.78033698541
5given(-0.99973246651, -0.0231093874844, -0.000975507746585), (0.0231093438431, -0.999732941886, 5.59865187623E-5), (-0.000976541043482, 3.34281965562E-5, 0.999999522625)139.65223156, 136.354138349, 7.24329285225
6given(-0.999777600324, 0.0209808554463, -0.00213391544516), (-0.0209814578689, -0.999779831094, 0.000260312652543), (-0.0021279840412, 0.000305027416102, 0.999997689318)136.629001062, 139.407864182, -7.10038192958
7given(0.999580000941, 0.0289740742215, 0.000569860910175), (-0.0289738242824, 0.999580072871, -0.000442069624718), (-0.000582430168237, 0.000425372906015, 0.999999739916)-2.01986257883, 2.06089555266, 9.63157543333
8given(0.99961160904, -0.0273243992135, 0.0054779814444), (0.027331736833, 0.999625612685, -0.00126910404541), (-0.00544125305206, 0.00141833388408, 0.999984190422)1.56236172666, -1.77254427739, -9.31457572516
9given(-0.999349778302, -0.03603451798, -0.00123859675991), (0.0360329913888, -0.99934983965, 0.00123350008911), (-0.00128224005455, 0.0011880676942, 0.999998472177)140.521609744, 135.372523777, 12.0092660181

-
Components

#1: Protein
Heterogeneous nuclear ribonucleoproteins A2/B1 / hnRNP A2/B1


Mass: 15391.775 Da / Num. of mol.: 10 / Fragment: LCD (UNP residues 193-353)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HNRNPA2B1, HNRPA2B1 / Production host: Escherichia coli (E. coli) / References: UniProt: P22626

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

-
Sample preparation

ComponentName: Fibrils of hnRNPA2 D290V LCD PM2 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 5000 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 36 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING ONLY
Helical symmertyAngular rotation/subunit: 179.6 ° / Axial rise/subunit: 2.44 Å / Axial symmetry: C1
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 14902 / Symmetry type: HELICAL
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 47.4 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0064010
ELECTRON MICROSCOPYf_angle_d0.5045360
ELECTRON MICROSCOPYf_dihedral_angle_d12.4821380
ELECTRON MICROSCOPYf_chiral_restr0.038360
ELECTRON MICROSCOPYf_plane_restr0.004800
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AELECTRON MICROSCOPYNCS constraints0.000521127055293
ens_1d_3AELECTRON MICROSCOPYNCS constraints0.000529634026552
ens_1d_4AELECTRON MICROSCOPYNCS constraints0.000519164717261
ens_1d_5AELECTRON MICROSCOPYNCS constraints0.000529412922367
ens_1d_6AELECTRON MICROSCOPYNCS constraints0.000507265849553
ens_1d_7AELECTRON MICROSCOPYNCS constraints0.000523727557416
ens_1d_8AELECTRON MICROSCOPYNCS constraints0.000520912537773
ens_1d_9AELECTRON MICROSCOPYNCS constraints0.000506148183587
ens_1d_10AELECTRON MICROSCOPYNCS constraints0.000541479314431

+
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