Publication | Science Advances

Team SNP

Insights into the structure and evolution of the human SAGA complex by affinity-ligand purification

 

The SNP team has just published an article entitled “Insights into the structure and evolution of the human SAGA complex by affinity-ligand purification” in Science Advances.

Human SAGA is a 20-subunit transcriptional coactivator. 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.

 

 

 

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Abstract figure
SAGA-­ specific adaptations enable SPL incorporation. (A) Comparison of human TAF5 [in TFiiD, blue; Protein Data Bank (PDB): 7EGE] and TAF5L (in SAGA, violet). The TAF5L helix interacting with TAF6L heAT repeat domain in SAGA is displaced compared to its counterpart in TAF5. (B) The same TAF5L helix forms a three-­ helix bundle with the heAT repeat domain of TAF6L (red) in SAGA. The contacts are shown with dotted lines. (C) TAF8 (orange) in TFiiD (PDB: 7EGE) interacts similarly with TAF6 as TAF5L (violet) with TAF6L (red) in SAGA. TAF6 heAT repeats were aligned on TAF6L heAT. Only TAF6L repeats are shown. (D) The last heAT repeat of TAF6L (red) deviates from the one of TAF6 (green; PDB: 7EGE) to allow the incorporation of the splicing module (SF3B3, light blue surface; SF3B5, dark blue surface) into SAGA. The last heAT repeat of TAF6 clashes with both SF3B3 and SF3B5.