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Title | The Saccharomyces cerevisiae Yta7 ATPase hexamer contains a unique bromodomain tier that functions in nucleosome disassembly. |
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Journal, issue, pages | J Biol Chem, Vol. 299, Issue 2, Page 102852, Year 2023 |
Publish date | Dec 30, 2022 |
Authors | Feng Wang / Xiang Feng / Qing He / Hua Li / Huilin Li / |
PubMed Abstract | The Saccharomyces cerevisiae Yta7 is a chromatin remodeler harboring a histone-interacting bromodomain (BRD) and two AAA+ modules. It is not well understood how Yta7 recognizes the histone H3 tail to ...The Saccharomyces cerevisiae Yta7 is a chromatin remodeler harboring a histone-interacting bromodomain (BRD) and two AAA+ modules. It is not well understood how Yta7 recognizes the histone H3 tail to promote nucleosome disassembly for DNA replication or RNA transcription. By cryo-EM analysis, here we show that Yta7 assembles a three-tiered hexamer with a top BRD tier, a middle AAA1 tier, and a bottom AAA2 tier. Unexpectedly, the Yta7 BRD stabilizes a four-stranded β-helix, termed BRD-interacting motif (BIM), of the largely disordered N-terminal region. The BIM motif is unique to the baker's yeast, and we show both BRD and BIM contribute to nucleosome recognition. We found that Yta7 binds both acetylated and nonacetylated H3 peptides but with a higher affinity for the unmodified peptide. This property is consistent with the absence of key residues of canonical BRDs involved in acetylated peptide recognition and the role of Yta7 in general nucleosome remodeling. Interestingly, the BRD tier exists in a spiral and a flat-ring form on top of the Yta7 AAA+ hexamer. The spiral is likely in a nucleosome-searching mode because the bottom BRD blocks the entry to the AAA+ chamber. The flat ring may be in a nucleosome disassembly state because the entry is unblocked and the H3 peptide has entered the AAA+ chamber and is stabilized by the AAA1 pore loops 1 and 2. Indeed, we show that the BRD tier is a flat ring when bound to the nucleosome. Overall, our study sheds light on the nucleosome disassembly by Yta7. |
External links | J Biol Chem / PubMed:36592926 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 10.0 Å |
Structure data | EMDB-26682: Cryo-EM structure of the S. cerevisiae chromatin remodeler Yta7 hexamer bound to ATPgS in state I EMDB-26695, PDB-7uqi: EMDB-26696, PDB-7uqj: EMDB-26697, PDB-7uqk: EMDB-28815: Cryo-EM of the S. cerevisiae chromatin remodeler Yta7 hexamer bound to nucleosome |
Chemicals | ChemComp-ADP: ChemComp-AGS: ChemComp-MG: |
Source |
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Keywords | TRANSFERASE / AAA+ ATPase / chromatin remodeler |