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- PDB-9rdk: Cryo-EM structure of the human SAGA co-activator complex -

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Entry
Database: PDB / ID: 9rdk
TitleCryo-EM structure of the human SAGA co-activator complex
Components
  • (Splicing factor 3B subunit ...) x 2
  • (Transcription ...) x 5
  • Ataxin-7
  • STAGA complex 65 subunit gamma
  • TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L
  • TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L
  • Transcriptional adapter 1
  • Transformation/transcription domain-associated protein
KeywordsTRANSCRIPTION / Transcription co-activator / Lysine acetyltransferase / complex
Function / homology
Function and homology information


SAGA-type complex / regulation of somatic stem cell population maintenance / SAGA complex assembly / lateral mesodermal cell differentiation / allantois development / transcription factor TFTC complex / SLIK (SAGA-like) complex / negative regulation of microtubule depolymerization / hepatocyte differentiation / Swr1 complex ...SAGA-type complex / regulation of somatic stem cell population maintenance / SAGA complex assembly / lateral mesodermal cell differentiation / allantois development / transcription factor TFTC complex / SLIK (SAGA-like) complex / negative regulation of microtubule depolymerization / hepatocyte differentiation / Swr1 complex / U12-type spliceosomal complex / RNA splicing, via transesterification reactions / maintenance of protein location in nucleus / splicing factor binding / regulation of double-strand break repair / U2-type precatalytic spliceosome / U2-type prespliceosome assembly / U2-type spliceosomal complex / RNA polymerase binding / SAGA complex / U2 snRNP / transcription preinitiation complex / precatalytic spliceosome / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / limb development / nucleus organization / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / regulation of RNA splicing / histone deacetylase complex / mRNA Splicing - Minor Pathway / DNA repair-dependent chromatin remodeling / NuA4 histone acetyltransferase complex / positive regulation of transcription initiation by RNA polymerase II / embryonic placenta development / U2 snRNA binding / somitogenesis / regulation of DNA repair / RNA polymerase II preinitiation complex assembly / positive regulation of double-strand break repair via homologous recombination / catalytic step 2 spliceosome / gastrulation / RNA Polymerase II Pre-transcription Events / mRNA Splicing - Major Pathway / visual perception / TBP-class protein binding / RNA splicing / nuclear estrogen receptor binding / male germ cell nucleus / spliceosomal complex / transcription coregulator activity / transcription initiation at RNA polymerase II promoter / DNA-templated transcription initiation / promoter-specific chromatin binding / G1/S transition of mitotic cell cycle / mRNA splicing, via spliceosome / Formation of the beta-catenin:TCF transactivating complex / negative regulation of protein catabolic process / mRNA transcription by RNA polymerase II / microtubule cytoskeleton organization / autophagy / multicellular organism growth / nuclear matrix / cytoplasmic ribonucleoprotein granule / transcription corepressor activity / nucleosome / HATs acetylate histones / microtubule cytoskeleton / positive regulation of cell growth / regulation of apoptotic process / transcription by RNA polymerase II / DNA-binding transcription factor binding / Regulation of TP53 Activity through Phosphorylation / transcription coactivator activity / regulation of cell cycle / Ub-specific processing proteases / nuclear speck / protein stabilization / chromatin remodeling / protein heterodimerization activity / focal adhesion / apoptotic process / regulation of transcription by RNA polymerase II / regulation of DNA-templated transcription / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / protein-containing complex binding / nucleolus / perinuclear region of cytoplasm / enzyme binding / negative regulation of transcription by RNA polymerase II / Golgi apparatus / positive regulation of transcription by RNA polymerase II
Similarity search - Function
STAGA complex 65 subunit gamma / : / Transcription factor Spt20 / Transcriptional coactivator Hfi1/Transcriptional adapter 1 / Spt20-like, SEP domain / Spt20, SEP domain / Transcriptional regulator of RNA polII, SAGA, subunit / SCA7 domain / SCA7, zinc-binding domain / SCA7 domain profile. ...STAGA complex 65 subunit gamma / : / Transcription factor Spt20 / Transcriptional coactivator Hfi1/Transcriptional adapter 1 / Spt20-like, SEP domain / Spt20, SEP domain / Transcriptional regulator of RNA polII, SAGA, subunit / SCA7 domain / SCA7, zinc-binding domain / SCA7 domain profile. / Tra1, HEAT repeat ring region / Tra1, HEAT repeat central region / Tra1 HEAT repeat central region / Tra1 HEAT repeat ring region / Transcription initiation factor IID, subunit 13 / : / Transcription initiation factor IID, 18kD subunit / Transcription initiation factor IID, 31kD subunit / Bromodomain transcription factors and PHD domain containing proteins / Transcription initiation factor TAFII31 / Bromodomain associated / Bromodomain associated domain / TFIID subunit TAF5, NTD2 domain superfamily / WD40 associated region in TFIID subunit, NTD2 domain / Transcription initiation factor TFIID subunit 12 / Transcription initiation factor TFIID subunit A / TATA box binding protein associated factor (TAF) / TFIID subunit TAF5, NTD2 domain / Transcription initiation factor TFIID subunit 6 / TAF6, C-terminal HEAT repeat domain superfamily / TAF6 C-terminal HEAT repeat domain / Transcription initiation factor TFIID subunit 12 domain / TAF6, C-terminal HEAT repeat domain / Transcription initiation factor TFIID 23-30kDa subunit / Transcription initiation factor TFIID, 23-30kDa subunit / Splicing factor 3B, subunit 5 / Splicing factor 3B subunit 5/RDS3 complex subunit 10 / Splicing factor 3B subunit 10 (SF3b10) / : / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / : / RSE1/DDB1/CPSF1 second beta-propeller / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / : / CPSF A subunit region / RSE1/DDB1/CPSF1 first beta-propeller / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone-fold / Armadillo-like helical / WD domain, G-beta repeat / Armadillo-type fold / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Ataxin-7 / Transcription initiation protein SPT3 homolog / TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L / STAGA complex 65 subunit gamma / Transcription initiation factor TFIID subunit 10 / Splicing factor 3B subunit 3 / Transcription initiation factor TFIID subunit 12 / Transcription factor SPT20 homolog / Transcriptional adapter 1 / Splicing factor 3B subunit 5 ...Ataxin-7 / Transcription initiation protein SPT3 homolog / TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L / STAGA complex 65 subunit gamma / Transcription initiation factor TFIID subunit 10 / Splicing factor 3B subunit 3 / Transcription initiation factor TFIID subunit 12 / Transcription factor SPT20 homolog / Transcriptional adapter 1 / Splicing factor 3B subunit 5 / Transcription initiation factor TFIID subunit 9B / Transformation/transcription domain-associated protein / TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.41 Å
AuthorsDamilot, M. / Ben-Shem, A. / Papai, G.
Funding support France, 2items
OrganizationGrant numberCountry
La ligue contre le cancer France
Agence Nationale de la Recherche (ANR)ANR-ATAC France
CitationJournal: Sci Adv / Year: 2026
Title: Insights into the structure and evolution of the human SAGA complex by affinity-ligand purification.
Authors: Mylène Damilot / Thomas Schoeps / Laszlo Tora / Patrick Schultz / Luc Lebeau / Gabor Papai / Adam Ben-Shem /
Abstract: Human SAGA is a 20-subunit transcriptional coactivator. Compared with yeast, metazoan SAGA uniquely incorporates a 150-kDa splicing-factor module (SPL), also present in U2 small nuclear ...Human SAGA is a 20-subunit transcriptional coactivator. Compared with yeast, metazoan SAGA uniquely incorporates a 150-kDa splicing-factor module (SPL), also present in U2 small nuclear ribonucleoprotein (U2snRNP). Metazoan gene duplication further specialized shared TFIID/SAGA subunits into SAGA-specific paralogs (TAF5L and TAF6L), but the functional consequences of this divergence are unknown. We report the structure of endogenous human SAGA purified via an affinity ligand from cells that were not disturbed by any genomic engineering tools. Our work reveals the high-resolution structure of SPL and the TAF6L HEAT repeat domain that provides the SPL with a docking surface. We elucidate how SPL and the HEAT repeats are incorporated into SAGA. We identify major structural differences between TAF6L/TAF5L and their canonical paralogs that enable SPL accommodation. SPL engages SAGA through a substantially smaller interface than in U2snRNP, despite sharing a deeply inserted helical motif. The seemingly weaker interaction of SPL with SAGA raises the possibility that SAGA relays this module to the splicing machinery.
History
DepositionJun 3, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 1, 2026Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
E: Transcription initiation factor TFIID subunit 9B
N: Ataxin-7
L: TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L
A: Splicing factor 3B subunit 3
C: Transformation/transcription domain-associated protein
D: STAGA complex 65 subunit gamma
G: Transcription initiation factor TFIID subunit 12
H: Transcription initiation factor TFIID subunit 10
I: Transcription initiation protein SPT3 homolog
J: Transcriptional adapter 1
K: TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L
M: Transcription factor SPT20 homolog
B: Splicing factor 3B subunit 5


Theoretical massNumber of molelcules
Total (without water)1,086,46813
Polymers1,086,46813
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

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Transcription ... , 5 types, 5 molecules EGHIM

#1: Protein Transcription initiation factor TFIID subunit 9B / Neuronal cell death-related protein 7 / DN-7 / Transcription initiation factor TFIID subunit 9-like ...Neuronal cell death-related protein 7 / DN-7 / Transcription initiation factor TFIID subunit 9-like / Transcription-associated factor TAFII31L


Mass: 27654.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9HBM6
#7: Protein Transcription initiation factor TFIID subunit 12 / Transcription initiation factor TFIID 20/15 kDa subunits / TAFII-20/TAFII-15 / TAFII20/TAFII15


Mass: 17948.467 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q16514
#8: Protein Transcription initiation factor TFIID subunit 10 / STAF28 / Transcription initiation factor TFIID 30 kDa subunit / TAF(II)30 / TAFII-30 / TAFII30


Mass: 21731.248 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q12962
#9: Protein Transcription initiation protein SPT3 homolog / SPT3-like protein


Mass: 35840.816 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O75486
#12: Protein Transcription factor SPT20 homolog / p38-interacting protein / p38IP


Mass: 85884.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q8NEM7

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Protein , 6 types, 6 molecules NLCDJK

#2: Protein Ataxin-7 / Spinocerebellar ataxia type 7 protein


Mass: 95597.742 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: O15265
#3: Protein TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L / TAF5L / PCAF-associated factor 65 beta / PAF65-beta


Mass: 66223.047 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: O75529
#5: Protein Transformation/transcription domain-associated protein / 350/400 kDa PCAF-associated factor / PAF350/400 / STAF40 / Tra1 homolog


Mass: 438139.531 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9Y4A5
#6: Protein STAGA complex 65 subunit gamma / Adenocarcinoma antigen ART1 / SPTF-associated factor 65 gamma / STAF65gamma / Suppressor of Ty 7-like


Mass: 46243.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: O94864
#10: Protein Transcriptional adapter 1 / SPT3-associated factor 42 / STAF42 / Transcriptional adapter 1-like protein


Mass: 37432.531 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q96BN2
#11: Protein TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L / TAF6L / PCAF-associated factor 65-alpha / PAF65-alpha


Mass: 67903.289 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9Y6J9

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Splicing factor 3B subunit ... , 2 types, 2 molecules AB

#4: Protein Splicing factor 3B subunit 3 / Pre-mRNA-splicing factor SF3b 130 kDa subunit / SF3b130 / STAF130 / Spliceosome-associated protein ...Pre-mRNA-splicing factor SF3b 130 kDa subunit / SF3b130 / STAF130 / Spliceosome-associated protein 130 / SAP 130


Mass: 135718.844 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q15393
#13: Protein Splicing factor 3B subunit 5 / SF3b5 / Pre-mRNA-splicing factor SF3b 10 kDa subunit


Mass: 10149.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9BWJ5

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Details

Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: SAGA / Type: COMPLEX / Entity ID: #4, #13, #5-#6, #1, #7-#11, #3, #12, #2 / Source: NATURAL
Molecular weightValue: 1.6 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human) / Strain: K562
Buffer solutionpH: 8
SpecimenConc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameCategory
1crYOLOparticle selection
2SerialEMimage acquisition
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1027610
3D reconstructionResolution: 2.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 272167 / Symmetry type: POINT

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