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TitleStructure of the human SAGA coactivator complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 12, Page 989-996, Year 2021
Publish dateNov 22, 2021
AuthorsDominik A Herbst / Meagan N Esbin / Robert K Louder / Claire Dugast-Darzacq / Gina M Dailey / Qianglin Fang / Xavier Darzacq / Robert Tjian / Eva Nogales /
PubMed AbstractThe SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are ...The SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.
External linksNat Struct Mol Biol / PubMed:34811519 / PubMed Central
MethodsEM (single particle)
Resolution2.93 - 19.09 Å
Structure data

EMDB-23027, PDB-7ktr:
Cryo-EM structure of the human SAGA coactivator complex (TRRAP, core)
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-23028, PDB-7kts:
Negative stain EM structure of the human SAGA coactivator complex (TRRAP, core, splicing module)
Method: EM (single particle) / Resolution: 19.09 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE / Phytic acid

Source
  • homo sapiens (human)
  • Human (human)
  • unclassified rhodococcus (bacteria)
KeywordsTRANSCRIPTION / coactivator / gene regulation / chromatin / splicing

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