8X32

The piccolo NuA4 bound to the H2A.Z nucleosome-H4KQ Complex with Ac-CoA at resetting state

Summary for 8X32

• Entry DOI: 10.2210/pdb8x32/pdb
• EMDB information: 38026
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,Chromatin modification-related protein EAF6, Chromatin modification-related protein, Histone acetyltransferase, ... (9 entities in total)
• Functional Keywords: nua4, nucleosome, gene regulation
• Biological source: Escherichia coli; More
• Total number of polymer chains: 14
• Total formula weight: 398762.25

Authors

Wang, L.,Zhang, H.,Zhu, H.,Zhu, P. (deposition date: 2023-11-10, release date: 2025-03-19, Last modification date: 2025-04-02)

Primary citation

Wang, L.,Zhang, H.,Jia, Q.,Li, W.,Yang, C.,Ma, L.,Li, M.,Lu, Y.,Zhu, H.,Zhu, P.
Cryo-EM structures reveal the acetylation process of piccolo NuA4.
Proc.Natl.Acad.Sci.USA, 122:e2414490122-e2414490122, 2025

PubMed Abstract: NuA4 is the only essential acetyltransferase in yeast that can catalyze the acetylation of the histones H2A, H2A.Z, and H4, thereby affecting gene transcription. However, the acetylation process of NuA4, such as how NuA4 acetylates H4 and H2A.Z differently, remains largely elusive. Here, using cryoelectron microscopy (cryo-EM) single particle analysis, we present seven cryo-EM structures of piccolo NuA4 (pNuA4) in complex with wild-type H2A.Z or H2A.Z-mutant-containing nucleosomes in the absence or presence of acetyl coenzyme A (Ac-CoA). We revealed that, in the absence of Ac-CoA, pNuA4 adopts multiple conformations to search for its substrates. After adding Ac-CoA, the single-molecule Förster resonance energy transfer (smFRET) and cryo-EM data indicated that pNuA4 prefers to bind H4 and undergoes a dynamic conformational change to complete the acetylation. We also obtained previously unseen structures in states associated with the acetylation of H2A.Z. These cryo-EM structures and smFRET results suggest a complex acetylation process on H4 and H2A.Z by pNuA4. The results provide a comprehensive picture of the mechanism by which pNuA4 acetylates its substrates within an H2A.Z-containing nucleosome.

PubMed: 40100634
DOI: 10.1073/pnas.2414490122

Experimental method

ELECTRON MICROSCOPY (4.4 Å)