IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v611y2022i7935d10.1038_s41586-022-05366-w.html
   My bibliography  Save this article

Bending forces and nucleotide state jointly regulate F-actin structure

Author

Listed:
  • Matthew J. Reynolds

    (The Rockefeller University)

  • Carla Hachicho

    (The Rockefeller University)

  • Ayala G. Carl

    (The Rockefeller University
    The Rockefeller University)

  • Rui Gong

    (The Rockefeller University)

  • Gregory M. Alushin

    (The Rockefeller University)

Abstract

ATP-hydrolysis-coupled actin polymerization is a fundamental mechanism of cellular force generation1–3. In turn, force4,5 and actin filament (F-actin) nucleotide state6 regulate actin dynamics by tuning F-actin’s engagement of actin-binding proteins through mechanisms that are unclear. Here we show that the nucleotide state of actin modulates F-actin structural transitions evoked by bending forces. Cryo-electron microscopy structures of ADP–F-actin and ADP-Pi–F-actin with sufficient resolution to visualize bound solvent reveal intersubunit interfaces bridged by water molecules that could mediate filament lattice flexibility. Despite extensive ordered solvent differences in the nucleotide cleft, these structures feature nearly identical lattices and essentially indistinguishable protein backbone conformations that are unlikely to be discriminable by actin-binding proteins. We next introduce a machine-learning-enabled pipeline for reconstructing bent filaments, enabling us to visualize both continuous structural variability and side-chain-level detail. Bent F-actin structures reveal rearrangements at intersubunit interfaces characterized by substantial alterations of helical twist and deformations in individual protomers, transitions that are distinct in ADP–F-actin and ADP-Pi–F-actin. This suggests that phosphate rigidifies actin subunits to alter the bending structural landscape of F-actin. As bending forces evoke nucleotide-state dependent conformational transitions of sufficient magnitude to be detected by actin-binding proteins, we propose that actin nucleotide state can serve as a co-regulator of F-actin mechanical regulation.

Suggested Citation

  • Matthew J. Reynolds & Carla Hachicho & Ayala G. Carl & Rui Gong & Gregory M. Alushin, 2022. "Bending forces and nucleotide state jointly regulate F-actin structure," Nature, Nature, vol. 611(7935), pages 380-386, November.
  • Handle: RePEc:nat:nature:v:611:y:2022:i:7935:d:10.1038_s41586-022-05366-w
    DOI: 10.1038/s41586-022-05366-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-05366-w
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-022-05366-w?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Kelli L. Hvorecny & Thomas E. Sladewski & Enrique M. Cruz & Justin M. Kollman & Aoife T. Heaslip, 2024. "Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Sai Shashank Chavali & Steven Z. Chou & Wenxiang Cao & Thomas D. Pollard & Enrique M. Cruz & Charles V. Sindelar, 2024. "Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Qianqian Ma & Wahyu Surya & Danxia He & Hanmeng Yang & Xiao Han & Mui Hoon Nai & Chwee Teck Lim & Jaume Torres & Yansong Miao, 2024. "Spa2 remodels ADP-actin via molecular condensation under glucose starvation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Chisato Tsuji & Marston Bradshaw & Megan F. Allen & Molly L. Jackson & Judith Mantell & Ufuk Borucu & Alastair W. Poole & Paul Verkade & Ingeborg Hers & Danielle M. Paul & Mark P. Dodding, 2024. "CryoET reveals actin filaments within platelet microtubules," Nature Communications, Nature, vol. 15(1), pages 1-8, 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:nature:v:611:y:2022:i:7935:d:10.1038_s41586-022-05366-w. 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.