IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41150-8.html
   My bibliography  Save this article

The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70

Author

Listed:
  • Lorea Velasco-Carneros

    (University of the Basque Country
    University of the Basque Country (UPV/EHU))

  • Jorge Cuéllar

    (National Centre for Biotechnology (CNB-CSIC))

  • Leire Dublang

    (University of the Basque Country
    University of the Basque Country (UPV/EHU))

  • César Santiago

    (National Centre for Biotechnology (CNB-CSIC))

  • Jean-Didier Maréchal

    (Universitat Autònoma de Barcelona, (UAB))

  • Jaime Martín-Benito

    (National Centre for Biotechnology (CNB-CSIC))

  • Moisés Maestro

    (National Centre for Biotechnology (CNB-CSIC))

  • José Ángel Fernández-Higuero

    (University of the Basque Country
    University of the Basque Country (UPV/EHU))

  • Natalia Orozco

    (University of the Basque Country)

  • Fernando Moro

    (University of the Basque Country
    University of the Basque Country (UPV/EHU))

  • José María Valpuesta

    (National Centre for Biotechnology (CNB-CSIC))

  • Arturo Muga

    (University of the Basque Country
    University of the Basque Country (UPV/EHU))

Abstract

J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.

Suggested Citation

  • Lorea Velasco-Carneros & Jorge Cuéllar & Leire Dublang & César Santiago & Jean-Didier Maréchal & Jaime Martín-Benito & Moisés Maestro & José Ángel Fernández-Higuero & Natalia Orozco & Fernando Moro & , 2023. "The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41150-8
    DOI: 10.1038/s41467-023-41150-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41150-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41150-8?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. Ofrah Faust & Meital Abayev-Avraham & Anne S. Wentink & Michael Maurer & Nadinath B. Nillegoda & Nir London & Bernd Bukau & Rina Rosenzweig, 2020. "HSP40 proteins use class-specific regulation to drive HSP70 functional diversity," Nature, Nature, vol. 587(7834), pages 489-494, November.
    2. Nadinath B. Nillegoda & Janine Kirstein & Anna Szlachcic & Mykhaylo Berynskyy & Antonia Stank & Florian Stengel & Kristin Arnsburg & Xuechao Gao & Annika Scior & Ruedi Aebersold & D. Lys Guilbride & R, 2015. "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation," Nature, Nature, vol. 524(7564), pages 247-251, August.
    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. Matthias M. Schneider & Saurabh Gautam & Therese W. Herling & Ewa Andrzejewska & Georg Krainer & Alyssa M. Miller & Victoria A. Trinkaus & Quentin A. E. Peter & Francesco Simone Ruggeri & Michele Vend, 2021. "The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Dezerae Cox & Ching-Seng Ang & Nadinath B. Nillegoda & Gavin E. Reid & Danny M. Hatters, 2022. "Hidden information on protein function in censuses of proteome foldedness," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Jaime Carrasco & Rosa Antón & Alejandro Valbuena & David Pantoja-Uceda & Mayur Mukhi & Rubén Hervás & Douglas V. Laurents & María Gasset & Javier Oroz, 2023. "Metamorphism in TDP-43 prion-like domain determines chaperone recognition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Yan Chen & Bin Tsai & Ningning Li & Ning Gao, 2022. "Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Sheng Chen & Anuradhika Puri & Braxton Bell & Joseph Fritsche & Hector H. Palacios & Maurie Balch & Macy L. Sprunger & Matthew K. Howard & Jeremy J. Ryan & Jessica N. Haines & Gary J. Patti & Albert A, 2024. "HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Eduardo Pinho Melo & Tasuku Konno & Ilaria Farace & Mosab Ali Awadelkareem & Lise R. Skov & Fernando Teodoro & Teresa P. Sancho & Adrienne W. Paton & James C. Paton & Matthew Fares & Pedro M. R. Paulo, 2022. "Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. S. M. Ayala Mariscal & M. L. Pigazzini & Y. Richter & M. Özel & I. L. Grothaus & J. Protze & K. Ziege & M. Kulke & M. ElBediwi & J. V. Vermaas & L. Colombi Ciacchi & S. Köppen & F. Liu & J. Kirstein, 2022. "Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    8. Kristine F. R. Pobre-Piza & Melissa J. Mann & Ashley R. Flory & Linda M. Hendershot, 2022. "Mapping SP-C co-chaperone binding sites reveals molecular consequences of disease-causing mutations on protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Rebecca San Gil & Dana Pascovici & Juliana Venturato & Heledd Brown-Wright & Prachi Mehta & Lidia Madrid San Martin & Jemma Wu & Wei Luan & Yi Kit Chui & Adekunle T. Bademosi & Shilpa Swaminathan & Se, 2024. "A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration," Nature Communications, Nature, vol. 15(1), pages 1-23, 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_s41467-023-41150-8. 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.