IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42229-y.html
   My bibliography  Save this article

Mechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins

Author

Listed:
  • Fred E. Fregoso

    (University of Pennsylvania
    University of Pennsylvania)

  • Malgorzata Boczkowska

    (University of Pennsylvania)

  • Grzegorz Rebowski

    (University of Pennsylvania)

  • Peter J. Carman

    (University of Pennsylvania
    University of Pennsylvania)

  • Trevor Eeuwen

    (The Rockefeller University)

  • Roberto Dominguez

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Cortactin coactivates Arp2/3 complex synergistically with WASP-family nucleation-promoting factors (NPFs) and stabilizes branched networks by linking Arp2/3 complex to F-actin. It is poorly understood how cortactin performs these functions. We describe the 2.89 Å resolution cryo-EM structure of cortactin’s N-terminal domain (Cort1-76) bound to Arp2/3 complex. Cortactin binds Arp2/3 complex through an inverted Acidic domain (D20-V29), which targets the same site on Arp3 as the Acidic domain of NPFs but with opposite polarity. Sequences N- and C-terminal to cortactin’s Acidic domain do not increase its affinity for Arp2/3 complex but contribute toward coactivation with NPFs. Coactivation further increases with NPF dimerization and for longer cortactin constructs with stronger binding to F-actin. The results suggest that cortactin contributes to Arp2/3 complex coactivation with NPFs in two ways, by helping recruit the complex to F-actin and by stabilizing the short-pitch (active) conformation, which are both byproducts of cortactin’s core function in branch stabilization.

Suggested Citation

  • Fred E. Fregoso & Malgorzata Boczkowska & Grzegorz Rebowski & Peter J. Carman & Trevor Eeuwen & Roberto Dominguez, 2023. "Mechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42229-y
    DOI: 10.1038/s41467-023-42229-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42229-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42229-y?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
    ---><---

    References listed on IDEAS

    as
    1. Siyang Guo & Olga S. Sokolova & Johnson Chung & Shae Padrick & Jeff Gelles & Bruce L. Goode, 2018. "Abp1 promotes Arp2/3 complex-dependent actin nucleation and stabilizes branch junctions by antagonizing GMF," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Malgorzata Boczkowska & Grzegorz Rebowski & David J. Kast & Roberto Dominguez, 2014. "Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    3. Katerina Naydenova & Christopher J. Russo, 2017. "Measuring the effects of particle orientation to improve the efficiency of electron cryomicroscopy," Nature Communications, Nature, vol. 8(1), pages 1-5, December.
    4. Florian Fäßler & Georgi Dimchev & Victor-Valentin Hodirnau & William Wan & Florian K. M. Schur, 2020. "Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    5. Fred E. Fregoso & Trevor Eeuwen & Gleb Simanov & Grzegorz Rebowski & Malgorzata Boczkowska & Austin Zimmet & Alexis M. Gautreau & Roberto Dominguez, 2022. "Molecular mechanism of Arp2/3 complex inhibition by Arpin," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Irene Dang & Roman Gorelik & Carla Sousa-Blin & Emmanuel Derivery & Christophe Guérin & Joern Linkner & Maria Nemethova & Julien G. Dumortier & Florence A. Giger & Tamara A. Chipysheva & Valeria D. Er, 2013. "Inhibitory signalling to the Arp2/3 complex steers cell migration," Nature, Nature, vol. 503(7475), pages 281-284, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Rayane Dibsy & Erwan Bremaud & Johnson Mak & Cyril Favard & Delphine Muriaux, 2023. "HIV-1 diverts cortical actin for particle assembly and release," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yanan Wang & Giovanni Chiappetta & Raphaël Guérois & Yijun Liu & Stéphane Romero & Daniel J. Boesch & Matthias Krause & Claire A. Dessalles & Avin Babataheri & Abdul I. Barakat & Baoyu Chen & Joelle V, 2023. "PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Radostin Danev & Matthew Belousoff & Yi-Lynn Liang & Xin Zhang & Fabian Eisenstein & Denise Wootten & Patrick M. Sexton, 2021. "Routine sub-2.5 Å cryo-EM structure determination of GPCRs," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Anjie Li & Tingting You & Xiaojie Pang & Yidi Wang & Lijin Tian & Xiaobo Li & Zhenfeng Liu, 2024. "Structural basis for an early stage of the photosystem II repair cycle in Chlamydomonas reinhardtii," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. 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.
    6. Tomáš Kovaľ & Nabajyoti Borah & Petra Sudzinová & Barbora Brezovská & Hana Šanderová & Viola Vaňková Hausnerová & Alena Křenková & Martin Hubálek & Mária Trundová & Kristýna Adámková & Jarmila Dušková, 2024. "Mycobacterial HelD connects RNA polymerase recycling with transcription initiation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    7. Sophie M. Travis & Brian P. Mahon & Wei Huang & Meisheng Ma & Michael J. Rale & Jodi Kraus & Derek J. Taylor & Rui Zhang & Sabine Petry, 2023. "Integrated model of the vertebrate augmin complex," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    8. Fred E. Fregoso & Trevor Eeuwen & Gleb Simanov & Grzegorz Rebowski & Malgorzata Boczkowska & Austin Zimmet & Alexis M. Gautreau & Roberto Dominguez, 2022. "Molecular mechanism of Arp2/3 complex inhibition by Arpin," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Rhianna J. Rowland & Svitlana Korolchuk & Marco Salamina & Natalie J. Tatum & James R. Ault & Sam Hart & Johan P. Turkenburg & James N. Blaza & Martin E. M. Noble & Jane A. Endicott, 2024. "Cryo-EM structure of the CDK2-cyclin A-CDC25A complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Anaïs Menny & Marie V. Lukassen & Emma C. Couves & Vojtech Franc & Albert J. R. Heck & Doryen Bubeck, 2021. "Structural basis of soluble membrane attack complex packaging for clearance," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    11. Kaitlyn M. Abe & Gan Li & Qixiang He & Timothy Grant & Ci Ji Lim, 2024. "Small LEA proteins mitigate air-water interface damage to fragile cryo-EM samples during plunge freezing," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    12. Pedro Rebelo-Guiomar & Simone Pellegrino & Kyle C. Dent & Aldema Sas-Chen & Leonor Miller-Fleming & Caterina Garone & Lindsey Van Haute & Jack F. Rogan & Adam Dinan & Andrew E. Firth & Byron Andrews &, 2022. "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. Hongcheng Fan & Bo Wang & Yan Zhang & Yun Zhu & Bo Song & Haijin Xu & Yujia Zhai & Mingqiang Qiao & Fei Sun, 2021. "A cryo-electron microscopy support film formed by 2D crystals of hydrophobin HFBI," Nature Communications, Nature, vol. 12(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-42229-y. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.