IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-24320-4.html
   My bibliography  Save this article

Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome

Author

Listed:
  • Li Wang

    (Key Laboratory for Protein Sciences of Ministry of Education, School of Life Science, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology & Beijing Frontier Research Center for Biological Structure, School of Life Science, Tsinghua University)

  • Kangjing Chen

    (Key Laboratory for Protein Sciences of Ministry of Education, School of Life Science, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology & Beijing Frontier Research Center for Biological Structure, School of Life Science, Tsinghua University)

  • Zhucheng Chen

    (Key Laboratory for Protein Sciences of Ministry of Education, School of Life Science, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology & Beijing Frontier Research Center for Biological Structure, School of Life Science, Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

Abstract

Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer.

Suggested Citation

  • Li Wang & Kangjing Chen & Zhucheng Chen, 2021. "Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24320-4
    DOI: 10.1038/s41467-021-24320-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-24320-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-24320-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Luka Bacic & Guillaume Gaullier & Jugal Mohapatra & Guanzhong Mao & Klaus Brackmann & Mikhail Panfilov & Glen Liszczak & Anton Sabantsev & Sebastian Deindl, 2024. "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Yichen Zhong & Hakimeh Moghaddas Sani & Bishnu P. Paudel & Jason K. K. Low & Ana P. G. Silva & Stefan Mueller & Chandrika Deshpande & Santosh Panjikar & Xavier J. Reid & Max J. Bedward & Antoine M. Oi, 2022. "The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Un Seng Chio & Eugene Palovcak & Anton A. A. Smith & Henriette Autzen & Elise N. Muñoz & Zanlin Yu & Feng Wang & David A. Agard & Jean-Paul Armache & Geeta J. Narlikar & Yifan Cheng, 2024. "Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24320-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.