9JAO

The structure of SMARCAD1 bound to the hexasome in the presence of ADP-BeFx

Summary for 9JAO

• Entry DOI: 10.2210/pdb9jao/pdb
• EMDB information: 61296
• Descriptor: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1, MAGNESIUM ION, Histone H3, ... (10 entities in total)
• Functional Keywords: dna, ligand, protein, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 374405.94

Authors

Chen, Z.C.,Hu, P.J.,Sia, Y.Y.,Chen, K.J.,Xia, X. (deposition date: 2024-08-25, release date: 2025-04-30, Last modification date: 2025-06-18)

Primary citation

Hu, P.,Sun, J.,Sun, H.,Chen, K.,Sia, Y.,Xia, X.,Xi, Q.,Chen, Z.
Subnucleosome preference of human chromatin remodeller SMARCAD1.
Nature, 2025

PubMed Abstract: Chromatin remodellers are pivotal in the regulation of nucleosome dynamics in cells, and they are important for chromatin packaging, transcription, replication and DNA repair. Here we show that the human chromatin remodeller SMARCAD1 exhibits a substrate preference for subnucleosomal particles over the canonical nucleosome. Cryo-electron microscopy structures of SMARCAD1 bound to the nucleosome and hexasome provide mechanistic insights into the substrate selectivity. SMARCAD1 binds to the hexasome through multiple family-specific elements that are essential for the functions in vitro and in cells. The enzyme binds to the canonical nucleosome in an inactive conformation, which accounts for its diminished activity towards the nucleosome. Notably, the histone chaperone FACT complex acts synergistically with H2A-H2B to promote the activity of SMARCAD1 in nucleosome remodelling. Together, our findings reveal an avenue for chromatin regulation, whereby subnucleosomes are remodelled through an ATP-dependent process.

PubMed: 40468067
DOI: 10.1038/s41586-025-09100-0

Experimental method

ELECTRON MICROSCOPY (3.1 Å)