9rdk | pdb_00009rdk
Cryo-EM structure of the human SAGA co-activator complex
Structural highlights
FunctionTAF9B_HUMAN Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.[1] Publication Abstract from PubMedHuman 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. Insights into the structure and evolution of the human SAGA complex by affinity-ligand purification.,Damilot M, Schoeps T, Tora L, Schultz P, Lebeau L, Papai G, Ben-Shem A Sci Adv. 2026 Mar 20;12(12):eaec8104. doi: 10.1126/sciadv.aec8104. Epub 2026 Mar , 18. PMID:41849588[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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