[English] 日本語
Yorodumi
- EMDB-47265: CoREST complex bound to U2AF2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-47265
TitleCoREST complex bound to U2AF2
Map data
Sample
  • Complex: Splicing factor U2AF2 bound to the CoREST complex made up of LSD1 and RCOR1
    • Protein or peptide: Lysine-specific histone demethylase 1A
    • Protein or peptide: REST corepressor 1
    • Protein or peptide: Splicing factor U2AF 65 kDa subunit
KeywordsRNA / splicing / melanoma / epigenetics / GENE REGULATION
Function / homology
Function and homology information


U2AF complex / poly-pyrimidine tract binding / pre-mRNA 3'-splice site binding / positive regulation of megakaryocyte differentiation / guanine metabolic process / : / protein demethylation / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity ...U2AF complex / poly-pyrimidine tract binding / pre-mRNA 3'-splice site binding / positive regulation of megakaryocyte differentiation / guanine metabolic process / : / protein demethylation / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity / telomeric repeat-containing RNA binding / histone H3K4 demethylase activity / muscle cell development / neuron maturation / positive regulation of neural precursor cell proliferation / mRNA 3'-end processing / C2H2 zinc finger domain binding / regulation of androgen receptor signaling pathway / MRF binding / commitment complex / Transport of Mature mRNA derived from an Intron-Containing Transcript / DNA repair complex / RNA Polymerase II Transcription Termination / negative regulation of DNA binding / U2-type prespliceosome / nuclear androgen receptor binding / regulation of double-strand break repair via homologous recombination / molecular function inhibitor activity / DNA repair-dependent chromatin remodeling / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of neuroblast proliferation / positive regulation of stem cell proliferation / spliceosomal complex assembly / Protein hydroxylation / histone H3K9 demethylase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of mRNA splicing, via spliceosome / histone deacetylase complex / positive regulation of cell size / histone demethylase activity / positive regulation of epithelial to mesenchymal transition / response to fungicide / cellular response to cAMP / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / negative regulation of protein ubiquitination / transcription repressor complex / mRNA Splicing - Major Pathway / negative regulation of protein binding / erythrocyte differentiation / : / positive regulation of RNA splicing / positive regulation of protein ubiquitination / Regulation of PTEN gene transcription / HDACs deacetylate histones / promoter-specific chromatin binding / spliceosomal complex / negative regulation of DNA-binding transcription factor activity / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / HDMs demethylate histones / cellular response to gamma radiation / cerebral cortex development / mRNA splicing, via spliceosome / positive regulation of neuron projection development / mRNA processing / transcription corepressor activity / cellular response to UV / p53 binding / chromatin organization / regulation of protein localization / flavin adenine dinucleotide binding / positive regulation of cold-induced thermogenesis / Factors involved in megakaryocyte development and platelet production / DNA-binding transcription factor binding / Estrogen-dependent gene expression / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / Potential therapeutics for SARS / chromosome, telomeric region / transcription coactivator activity / oxidoreductase activity / nuclear speck / chromatin remodeling / negative regulation of gene expression / negative regulation of DNA-templated transcription / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / nucleoplasm / identical protein binding / nucleus
Similarity search - Function
U2 snRNP auxilliary factor, large subunit, splicing factor / : / Helical region in REST corepressor / : / Histone lysine-specific demethylase / ELM2 domain / ELM2 domain / ELM2 domain profile. / ELM2 / SWIRM domain ...U2 snRNP auxilliary factor, large subunit, splicing factor / : / Helical region in REST corepressor / : / Histone lysine-specific demethylase / ELM2 domain / ELM2 domain / ELM2 domain profile. / ELM2 / SWIRM domain / SWIRM domain / SWIRM domain profile. / : / SANT domain profile. / SANT domain / Amine oxidase / Flavin containing amine oxidoreductase / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Homeobox-like domain superfamily / FAD/NAD(P)-binding domain superfamily / Nucleotide-binding alpha-beta plait domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
Lysine-specific histone demethylase 1A / Splicing factor U2AF 65 kDa subunit / REST corepressor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 5.14 Å
AuthorsHicks CW / Alani RM
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private#1045461 United States
CitationJournal: bioRxiv / Year: 2024
Title: CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.
Authors: Robert J Fisher / Kihyun Park / Kwangwoon Lee / Katarina Pinjusic / Allison Vanasse / Christina S Ennis / Scott Ficcaro / Jarrod Marto / Stephanie Stransky / Joseph Duke-Cohan / Anupa ...Authors: Robert J Fisher / Kihyun Park / Kwangwoon Lee / Katarina Pinjusic / Allison Vanasse / Christina S Ennis / Scott Ficcaro / Jarrod Marto / Stephanie Stransky / Joseph Duke-Cohan / Anupa Geethadevi / Eric Raabe / Simone Sidoli / Chad W Hicks / Derin B Keskin / Catherine J Wu / Philip A Cole / Rhoda M Alani
Abstract: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions ...Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies. Using predictive machine learning models and MHC IP-MS, we identify thousands of corin-induced neopeptides derived from unannotated splice sites which generate immunogenic splice-neoantigens. Furthermore, corin reactivates the response to immune checkpoint blockade and promotes dramatic expansion of cytotoxic T cells in an immune cold melanoma model. CoREST complex inhibition thus represents a unique therapeutic opportunity in cancer which creates tumor-associated neoantigens that enhance the immunogenicity of current therapeutics.
STATEMENT OF SIGNIFICANCE: We identify a novel role of the CoREST transcriptional repressor complex in regulating pre-mRNA splicing and find that the small molecule inhibitor, corin, promotes ...STATEMENT OF SIGNIFICANCE: We identify a novel role of the CoREST transcriptional repressor complex in regulating pre-mRNA splicing and find that the small molecule inhibitor, corin, promotes alternative splicing events in cancer leading to neoantigen expression and T cell-mediated immunity. This represents a potential approach to promote immunoreactive neoantigen expression in immune-cold tumors.
History
DepositionOct 10, 2024-
Header (metadata) releaseJan 8, 2025-
Map releaseJan 8, 2025-
UpdateJan 8, 2025-
Current statusJan 8, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_47265.png

Downloads & links

-
Map

FileDownload / File: emd_47265.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.9 Å/pix.
x 360 pix.
= 324. Å		0.9 Å/pix.
x 360 pix.
= 324. Å		0.9 Å/pix.
x 360 pix.
= 324. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.9 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.07
Minimum - Maximum-0.18983932 - 0.26469925
Average (Standard dev.)-0.00007972844 (±0.005987911)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 324.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_47265_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_47265_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_47265_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Splicing factor U2AF2 bound to the CoREST complex made up of LSD1...

EntireName: Splicing factor U2AF2 bound to the CoREST complex made up of LSD1 and RCOR1
Components
  • Complex: Splicing factor U2AF2 bound to the CoREST complex made up of LSD1 and RCOR1
    • Protein or peptide: Lysine-specific histone demethylase 1A
    • Protein or peptide: REST corepressor 1
    • Protein or peptide: Splicing factor U2AF 65 kDa subunit

-
Supramolecule #1: Splicing factor U2AF2 bound to the CoREST complex made up of LSD1...

SupramoleculeName: Splicing factor U2AF2 bound to the CoREST complex made up of LSD1 and RCOR1
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Lysine-specific histone demethylase 1A

MacromoleculeName: Lysine-specific histone demethylase 1A / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: Oxidoreductases
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 74.126781 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: PSGVEGAAFQ SRLPHDRMTS QEAACFPDII SGPQQTQKVF LFIRNRTLQL WLDNPKIQLT FEATLQQLEA PYNSDTVLVH RVHSYLERH GLINFGIYKR IKPLPTKKTG KVIIIGSGVS GLAAARQLQS FGMDVTLLEA RDRVGGRVAT FRKGNYVADL G AMVVTGLG ...String:
PSGVEGAAFQ SRLPHDRMTS QEAACFPDII SGPQQTQKVF LFIRNRTLQL WLDNPKIQLT FEATLQQLEA PYNSDTVLVH RVHSYLERH GLINFGIYKR IKPLPTKKTG KVIIIGSGVS GLAAARQLQS FGMDVTLLEA RDRVGGRVAT FRKGNYVADL G AMVVTGLG GNPMAVVSKQ VNMELAKIKQ KCPLYEANGQ AVPKEKDEMV EQEFNRLLEA TSYLSHQLDF NVLNNKPVSL GQ ALEVVIQ LQEKHVKDEQ IEHWKKIVKT QEELKELLNK MVNLKEKIKE LHQQYKEASE VKPPRDITAE FLVKSKHRDL TAL CKEYDE LAETQGKLEE KLQELEANPP SDVYLSSRDR QILDWHFANL EFANATPLST LSLKHWDQDD DFEFTGSHLT VRNG YSCVP VALAEGLDIK LNTAVRQVRY TASGCEVIAV NTRSTSQTFI YKCDAVLCTL PLGVLKQQPP AVQFVPPLPE WKTSA VQRM GFGNLNKVVL CFDRVFWDPS VNLFGHVGST TASRGELFLF WNLYKAPILL ALVAGEAAGI MENISDDVIV GRCLAI LKG IFGSSAVPQP KETVVSRWRA DPWARGSYSY VAAGSSGNDY DLMAQPITPG PSIPGAPQPI PRLFFAGEHT IRNYPAT VH GALLSGLREA GRIADQFLGA MYTL

UniProtKB: Lysine-specific histone demethylase 1A

-
Macromolecule #2: REST corepressor 1

MacromoleculeName: REST corepressor 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.675833 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
RKPPKGMFLS QEDVEAVSAN ATAATTVLRQ LDMELVSVKR QIQNIKQTNS ALKEKLDGGI EPYRLPEVI

UniProtKB: REST corepressor 1

-
Macromolecule #3: Splicing factor U2AF 65 kDa subunit

MacromoleculeName: Splicing factor U2AF 65 kDa subunit / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 8.64186 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
SAHKLFIGGL PNYLNDDQVK ELLTSFGPLK AFNLVKDSAT GLSKGYAFCE YVDINVTDQA IAGLNGMQLG DKKLLVQRAS

UniProtKB: Splicing factor U2AF 65 kDa subunit

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 200 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

+
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 5.14 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 172429
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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