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TitleStructure of the transcriptional co-activator SAGA complex, including the histone acetyltransferase module.
Journal, issue, pagesMol Cell, Vol. 85, Issue 23, Page 4333-44346.e4, Year 2025
Publish dateDec 4, 2025
AuthorsRayees U H Mattoo / Dong-Hua Chen / David A Bushnell / Sagi Tamir / Roger D Kornberg /
PubMed AbstractThe Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, a 1.8 MDa multi-subunit assembly comprising 19 subunits, is required for RNA polymerase II transcription in eukaryotes. The complex consists of four ...The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, a 1.8 MDa multi-subunit assembly comprising 19 subunits, is required for RNA polymerase II transcription in eukaryotes. The complex consists of four modules: transcription-associated protein 1 (Tra1), core, deubiquitination (DUB), and histone acetyltransferase (HAT). Although the structures of the Tra1, core, and DUB modules have been determined, the overall architecture of the HAT module remained elusive due to its inherent flexibility. To address this, we conducted cryo-electron microscopy (cryo-EM) analyses on SAGA purified from the thermophilic fungus Chaetomium thermophilum, yielding structures of Tra1 and core modules at 2.6 Å and three of the four HAT subunits at 3.7 Å. The structure of the HAT module was informative about the aspects of histone acetylation and the interface of HAT-core modules, contradicting earlier AlphaFold predictions. Our structure-guided genetic and biochemical analyses confirmed the roles of Ada1 and Spt7 in anchoring the HAT module within the SAGA complex.
External linksMol Cell / PubMed:41260211 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 4.4 Å
Structure data

EMDB-73233, PDB-9ynu:
Tra1 and core modules including core tip of ctSAGA complex
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-73234: Tra1 and Core Module of ctSAGA
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-73235, PDB-9ynv:
Histone Acetyl Transferase (HAT) module of ctSAGA
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-73236, PDB-9ynw:
Tra1, Core and minimal HAT modules of ctSAGA, composite.
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-73237: Focused map of HAT module Bromodomain region
PDB-9yzy: ctSAGA Focused on HAT Bromodomain region
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-73238: Focused map of Tra1 module of ctSAGA
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-73239: Focused map of Tra1 module of ctSAGA
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-73240: Focused map of Tra1 module of ctSAGA complex
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-73241: Focused map of core module of ctSAGA complex
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-73242: Focused map of core module of ctSAGA complex
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-73243: Focused map of core module of ctSAGA complex
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-73261, PDB-9yol:
Tra1 module of ctSAGA
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-73269, PDB-9yoq:
Core module of ctSAGA
Method: EM (single particle) / Resolution: 2.6 Å

Source
  • thermochaetoides thermophila (fungus)
KeywordsTRANSCRIPTION / ctSAGA complex / Histone Acetyl Transferase (HAT) Module / Tra1 module and Core module

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