9C57

Reconstituted P400 Subcomplex of the human TIP60 complex

Summary for 9C57

• Entry DOI: 10.2210/pdb9c57/pdb
• EMDB information: 45206
• Descriptor: RuvB-like 1, ADENOSINE-5'-TRIPHOSPHATE, Enhancer of polycomb homolog 1, ... (10 entities in total)
• Functional Keywords: complex, chromatin regulator, gene regulation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 976735.88

Authors

Yang, Z.,Mameri, A.,Florez Ariza, A.J.,Cote, J.,Nogales, E. (deposition date: 2024-06-05, release date: 2024-08-21, Last modification date: 2024-09-11)

Primary citation

Yang, Z.,Mameri, A.,Cattoglio, C.,Lachance, C.,Florez Ariza, A.J.,Luo, J.,Humbert, J.,Sudarshan, D.,Banerjea, A.,Galloy, M.,Fradet-Turcotte, A.,Lambert, J.P.,Ranish, J.A.,Cote, J.,Nogales, E.
Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.
Science, 385:eadl5816-eadl5816, 2024

PubMed Abstract: The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the E1A binding protein P400 (EP400) subunit serves as a scaffold holding the different functional modules in specific positions, creating a distinct arrangement of the actin-related protein (ARP) module. EP400 interacts with the transformation/transcription domain-associated protein (TRRAP) subunit by using a footprint that overlaps with that of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.

PubMed: 39088653
DOI: 10.1126/science.adl5816

Experimental method

ELECTRON MICROSCOPY (2.75 Å)