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- EMDB-19853: Structure of the human INTS5/8/10/15 subcomplex -

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Basic information

Entry
Database: EMDB / ID: EMD-19853
TitleStructure of the human INTS5/8/10/15 subcomplex
Map data
Sample
  • Complex: Structure of INTS5/8/10/15 subcomplex
    • Protein or peptide: Integrator complex subunit 15
    • Protein or peptide: Integrator complex subunit 10
    • Protein or peptide: Integrator complex subunit 8
    • Protein or peptide: Integrator complex subunit 5
KeywordsIntegrator complex / RNA polymerase II transcription termination / transcription factors / TRANSCRIPTION
Function / homology
Function and homology information


snRNA 3'-end processing / snRNA processing / integrator complex / regulation of transcription elongation by RNA polymerase II / RNA polymerase II transcribes snRNA genes / nuclear membrane / nucleoplasm / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function
Integrator complex subunit 10 / Integrator complex subunit 15 / Integrator complex subunit 5, C-terminal / Integrator complex subunit 5, N-terminal / Integrator complex subunit 8 / Integrator complex subunit 5 / Integrator complex subunit 5 N-terminus / Integrator complex subunit 5 C-terminus / Integrator complex subunit 15 / Integrator subunit 10 / Tetratricopeptide-like helical domain superfamily
Similarity search - Domain/homology
Integrator complex subunit 5 / Integrator complex subunit 8 / Integrator complex subunit 15 / Integrator complex subunit 10
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.7 Å
AuthorsRazew M / Galej WP
Funding support Germany, 1 items
OrganizationGrant numberCountry
EIPOD fellowship under Marie Sklodowska-Curie Actions COFUND Germany
CitationJournal: Mol Cell / Year: 2024
Title: Structural basis of the Integrator complex assembly and association with transcription factors.
Authors: Michal Razew / Angelique Fraudeau / Moritz M Pfleiderer / Romain Linares / Wojciech P Galej /
Abstract: Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This is achieved via two enzymatic activities, RNA endonuclease and ...Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This is achieved via two enzymatic activities, RNA endonuclease and protein phosphatase, acting on the promoter-proximally paused RNA polymerase Ⅱ (RNAPⅡ). Yet, it remains unclear how Integrator assembly and recruitment are regulated and what the functions of many of its core subunits are. Here, we report the structures of two human Integrator sub-complexes: INTS10/13/14/15 and INTS5/8/10/15, and an integrative model of the fully assembled Integrator bound to the RNAPⅡ paused elongating complex (PEC). An in silico protein-protein interaction screen of over 1,500 human transcription factors (TFs) identified ZNF655 as a direct interacting partner of INTS13 within the fully assembled Integrator. We propose a model wherein INTS13 acts as a platform for the recruitment of TFs that could modulate the stability of the Integrator's association at specific loci and regulate transcription attenuation of the target genes.
History
DepositionMar 14, 2024-
Header (metadata) releaseJun 12, 2024-
Map releaseJun 12, 2024-
UpdateJul 24, 2024-
Current statusJul 24, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_19853.png

Downloads & links

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Map

FileDownload / File: emd_19853.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.02 Å/pix.
x 256 pix.
= 516. Å		2.02 Å/pix.
x 256 pix.
= 516. Å		2.02 Å/pix.
x 256 pix.
= 516. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.01563 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0633
Minimum - Maximum-0.35274842 - 1.0665693
Average (Standard dev.)0.00082430977 (±0.01645849)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 516.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_19853_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_19853_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : Structure of INTS5/8/10/15 subcomplex

EntireName: Structure of INTS5/8/10/15 subcomplex
Components
  • Complex: Structure of INTS5/8/10/15 subcomplex
    • Protein or peptide: Integrator complex subunit 15
    • Protein or peptide: Integrator complex subunit 10
    • Protein or peptide: Integrator complex subunit 8
    • Protein or peptide: Integrator complex subunit 5

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Supramolecule #1: Structure of INTS5/8/10/15 subcomplex

SupramoleculeName: Structure of INTS5/8/10/15 subcomplex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Integrator complex subunit 15

MacromoleculeName: Integrator complex subunit 15 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 50.102402 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MSDIRHSLLR RDALSAAKEV LYHLDIYFSS QLQSAPLPIV DKGPVELLEE FVFQVPKERS AQPKRLNSLQ ELQLLEIMCN YFQEQTKDS VRQIIFSSLF SPQGNKADDS RMSLLGKLVS MAVAVCRIPV LECAASWLQR TPVVYCVRLA KALVDDYCCL V PGSIQTLK ...String:
MSDIRHSLLR RDALSAAKEV LYHLDIYFSS QLQSAPLPIV DKGPVELLEE FVFQVPKERS AQPKRLNSLQ ELQLLEIMCN YFQEQTKDS VRQIIFSSLF SPQGNKADDS RMSLLGKLVS MAVAVCRIPV LECAASWLQR TPVVYCVRLA KALVDDYCCL V PGSIQTLK QIFSASPRFC CQFITSVTAL YDLSSDDLIP PMDLLEMIVT WIFEDPRLIL ITFLNTPIAA NLPIGFLELT PL VGLIRWC VKAPLAYKRK KKPPLSNGHV SNKVTKDPGV GMDRDSHLLY SKLHLSVLQV LMTLQLHLTE KNLYGRLGLI LFD HMVPLV EEINRLADEL NPLNASQEIE LSLDRLAQAL QVAMASGALL CTRDDLRTLC SRLPHNNLLQ LVISGPVQQS PHAA LPPGF YPHIHTPPLG YGAVPAHPAA HPALPTHPGH TFISGVTFPF RPIR

UniProtKB: Integrator complex subunit 15

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Macromolecule #2: Integrator complex subunit 10

MacromoleculeName: Integrator complex subunit 10 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 82.339867 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MSAQGDCEFL VQRARELVPQ DLWAAKAWLI TARSLYPADF NIQYEMYTIE RNAERTATAG RLLYDMFVNF PDQPVVWREI SIITSALRN DSQDKQTQFL RSLFETLPGR VQCEMLLKVT EQCFNTLERS EMLLLLLRRF PETVVQHGVG LGEALLEAET I EEQESPVN ...String:
MSAQGDCEFL VQRARELVPQ DLWAAKAWLI TARSLYPADF NIQYEMYTIE RNAERTATAG RLLYDMFVNF PDQPVVWREI SIITSALRN DSQDKQTQFL RSLFETLPGR VQCEMLLKVT EQCFNTLERS EMLLLLLRRF PETVVQHGVG LGEALLEAET I EEQESPVN CFRKLFVCDV LPLIINNHDV RLPANLLYKY LNKAAEFYIN YVTRSTQIEN QHQGAQDTSD LMSPSKRSSQ KY IIEGLTE KSSQIVDPWE RLFKILNVVG MRCEWQMDKG RRSYGDILHR MKDLCRYMNN FDSEAHAKYK NQVVYSTMLV FFK NAFQYV NSIQPSLFQG PNAPSQVPLV LLEDVSNVYG DVEIDRNKHI HKKRKLAEGR EKTMSSDDED CSAKGRNRHI VVNK AELAN STEVLESFKL ARESWELLYS LEFLDKEFTR ICLAWKTDTW LWLRIFLTDM IIYQGQYKKA IASLHHLAAL QGSIS QPQI TGQGTLEHQR ALIQLATCHF ALGEYRMTCE KVLDLMCYMV LPIQDGGKSQ EEPSKVKPKF RKGSDLKLLP CTSKAI MPY CLHLMLACFK LRAFTDNRDD MALGHVIVLL QQEWPRGENL FLKAVNKICQ QGNFQYENFF NYVTNIDMLE EFAYLRT QE GGKIHLELLP NQGMLIKHHT VTRGITKGVK EDFRLAMERQ VSRCGENLMV VLHRFCINEK ILLLQTLT

UniProtKB: Integrator complex subunit 10

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Macromolecule #3: Integrator complex subunit 8

MacromoleculeName: Integrator complex subunit 8 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 113.219859 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MSAEAADREA ATSSRPCTPP QTCWFEFLLE ESLLEKHLRK PCPDPAPVQL IVQFLEQASK PSVNEQNQVQ PPPDNKRNRI LKLLALKVA AHLKWDLDIL EKSLSVPVLN MLLNELLCIS KVPPGTKHVD MDLATLPPTT AMAVLLYNRW AIRTIVQSSF P VKQAKPGP ...String:
MSAEAADREA ATSSRPCTPP QTCWFEFLLE ESLLEKHLRK PCPDPAPVQL IVQFLEQASK PSVNEQNQVQ PPPDNKRNRI LKLLALKVA AHLKWDLDIL EKSLSVPVLN MLLNELLCIS KVPPGTKHVD MDLATLPPTT AMAVLLYNRW AIRTIVQSSF P VKQAKPGP PQLSVMNQMQ QEKELTENIL KVLKEQAADS ILVLEAALKL NKDLYVHTMR TLDLLAMEPG MVNGETESST AG LKVKTEE MQCQVCYDLG AAYFQQGSTN SAVYENAREK FFRTKELIAE IGSLSLHCTI DEKRLAGYCQ ACDVLVPSSD STS QQLTPY SQVHICLRSG NYQEVIQIFI EDNLTLSLPV QFRQSVLREL FKKAQQGNEA LDEICFKVCA CNTVRDILEG RTIS VQFNQ LFLRPNKEKI DFLLEVCSRS VNLEKASESL KGNMAAFLKN VCLGLEDLQY VFMISSHELF ITLLKDEERK LLVDQ MRKR SPRVNLCIKP VTSFYDIPAS ASVNIGQLEH QLILSVDPWR IRQILIELHG MTSERQFWTV SNKWEVPSVY SGVILG IKD NLTRDLVYIL MAKGLHCSTV KDFSHAKQLF AACLELVTEF SPKLRQVMLN EMLLLDIHTH EAGTGQAGER PPSDLIS RV RGYLEMRLPD IPLRQVIAEE CVAFMLNWRE NEYLTLQVPA FLLQSNPYVK LGQLLAATCK ELPGPKESRR TAKDLWEV V VQICSVSSQH KRGNDGRVSL IKQRESTLGI MYRSELLSFI KKLREPLVLT IILSLFVKLH NVREDIVNDI TAEHISIWP SSIPNLQSVD FEAVAITVKE LVRYTLSINP NNHSWLIIQA DIYFATNQYS AALHYYLQAG AVCSDFFNKA VPPDVYTDQV IKRMIKCCS LLNCHTQVAI LCQFLREIDY KTAFKSLQEQ NSHDAMDSYY DYIWDVTILE YLTYLHHKRG ETDKRQIAIK A IGQTELNA SNPEEVLQLA AQRRKKKFLQ AMAKLYF

UniProtKB: Integrator complex subunit 8

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Macromolecule #4: Integrator complex subunit 5

MacromoleculeName: Integrator complex subunit 5 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 108.115227 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MSALCDPPGA PGPPGPAPAT HGPAPLSAQE LSQEIKAFLT GVDPILGHQL SAREHARCGL LLLRSLPPAR AAVLDHLRGV FDESVRAHL AALDETPVAG PPHLRPPPPS HVPAGGPGLE DVVQEVQQVL SEFIRANPKA WAPVISAWSI DLMGQLSSTY S GQHQRVPH ...String:
MSALCDPPGA PGPPGPAPAT HGPAPLSAQE LSQEIKAFLT GVDPILGHQL SAREHARCGL LLLRSLPPAR AAVLDHLRGV FDESVRAHL AALDETPVAG PPHLRPPPPS HVPAGGPGLE DVVQEVQQVL SEFIRANPKA WAPVISAWSI DLMGQLSSTY S GQHQRVPH ATGALNELLQ LWMGCRATRT LMDIYVQCLS ALIGSCPDAC VDALLDTSVQ HSPHFDWVVA HIGSSFPGTI IS RVLSCGL KDFCVHGGAG GGAGSSGGSS SQTPSTDPFP GSPAIPAEKR VPKIASVVGI LGHLASRHGD SIRRELLRMF HDS LAGGSG GRSGDPSLQA TVPFLLQLAV MSPALLGTVS GELVDCLKPP AVLSQLQQHL QGFPREELDN MLNLAVHLVS QASG AGAYR LLQFLVDTAM PASVITTQGL AVPDTVREAC DRLIQLLLLH LQKLVHHRGG SPGEGVLGPP PPPRLVPFLD ALKNH VGEL CGETLRLERK RFLWQHQLLG LLSVYTRPSC GPEALGHLLS RARSPEELSL ATQLYAGLVV SLSGLLPLAF RSCLAR VHA GTLQPPFTAR FLRNLALLVG WEQQGGEGPA ALGAHFGESA SAHLSDLAPL LLHPEEEVAE AAASLLAICP FPSEALS PS QLLGLVRAGV HRFFASLRLH GPPGVASACQ LLTRLSQTSP AGLKAVLQLL VEGALHRGNT ELFGGQVDGD NETLSVVS A SLASASLLDT NRRHTAAVPG PGGIWSVFHA GVIGRGLKPP KFVQSRNQQE VIYNTQSLLS LLVHCCSAPG GTECGECWG APILSPEAAK AVAVTLVESV CPDAAGAELA WPPEEHARAT VERDLRIGRR FREQPLLFEL LKLVAAAPPA LCYCSVLLRG LLAALLGHW EASRHPDTTH SPWHLEASCT LVAVMAEGSL LPPALGNMHE VFSQLAPFEV RLLLLSVWGF LREHGPLPQK F IFQSERGR FIRDFSREGG GEGGPHLAVL HSVLHRNIDR LGLFSGRFQA PSPSTLLRQG T

UniProtKB: Integrator complex subunit 5

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 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: 0.8 µm

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7pks

Final reconstructionResolution.type: BY AUTHOR / Resolution: 7.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 65387
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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