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Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex

Author

Listed:
  • Avinash B. Patel

    (Northwestern University)

  • Jinkang Qing

    (Northwestern University
    Northwestern University)

  • Kelly H. Tam

    (Northwestern University)

  • Sara Zaman

    (Northwestern University)

  • Maria Luiso

    (Northwestern University)

  • Ishwar Radhakrishnan

    (Northwestern University)

  • Yuan He

    (Northwestern University)

Abstract

The Rpd3L histone deacetylase (HDAC) complex is an ancient 12-subunit complex conserved in a broad range of eukaryotes that performs localized deacetylation at or near sites of recruitment by DNA-bound factors. Here we describe the cryo-EM structure of this prototypical HDAC complex that is characterized by as many as seven subunits performing scaffolding roles for the tight integration of the only catalytic subunit, Rpd3. The principal scaffolding protein, Sin3, along with Rpd3 and the histone chaperone, Ume1, are present in two copies, with each copy organized into separate lobes of an asymmetric dimeric molecular assembly. The active site of one Rpd3 is completely occluded by a leucine side chain of Rxt2, while the tips of the two lobes and the more peripherally associated subunits exhibit varying levels of flexibility and positional disorder. The structure reveals unexpected structural homology/analogy between unrelated subunits in the fungal and mammalian complexes and provides a foundation for deeper interrogations of structure, biology, and mechanism of these complexes, as well as for the discovery of HDAC complex-specific inhibitors.

Suggested Citation

  • Avinash B. Patel & Jinkang Qing & Kelly H. Tam & Sara Zaman & Maria Luiso & Ishwar Radhakrishnan & Yuan He, 2023. "Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38687-z
    DOI: 10.1038/s41467-023-38687-z
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    References listed on IDEAS

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    1. Stephen E. Rundlett & Andrew A. Carmen & Noriyuki Suka & Bryan M. Turner & Michael Grunstein, 1998. "Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3," Nature, Nature, vol. 392(6678), pages 831-835, April.
    2. Michael Grunstein, 1997. "Histone acetylation in chromatin structure and transcription," Nature, Nature, vol. 389(6649), pages 349-352, September.
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    Cited by:

    1. Jonathan W. Markert & Seychelle M. Vos & Lucas Farnung, 2023. "Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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