IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54647-7.html
   My bibliography  Save this article

Dynamic fibrillar assembly of αB-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM

Author

Listed:
  • Russell McFarland

    (Oregon Health & Science University
    Oregon Health & Science University
    Portland State University
    KBI Biopharma)

  • Rozhan Noroozi

    (Oregon Health & Science University
    Oregon Health & Science University)

  • Adam P. Miller

    (Oregon Health & Science University
    Oregon Health & Science University)

  • Steve L. Reichow

    (Oregon Health & Science University
    Oregon Health & Science University
    Portland State University)

Abstract

αB-crystallin is an archetypical member of the small heat shock proteins (sHSPs) vital for cellular proteostasis and mitigating protein misfolding diseases. Gaining insights into the principles defining their molecular organization and chaperone function have been hindered by intrinsic dynamic properties and limited high-resolution structural analysis. To disentangle the mechanistic underpinnings of these dynamical properties, we ablate a conserved IXI-motif located within the N-terminal (NT) domain of human αB-crystallin implicated in subunit exchange dynamics and client sequestration. This results in a profound structural transformation, from highly polydispersed caged-like native assemblies into an elongated fibril state amenable to high-resolution cryo-EM analysis. The reversible nature of this variant facilitates interrogation of functional effects due to perturbation of the NT-IXI motif in both the native-like oligomer and fibril states. Together, our investigations unveil several features thought to be key mechanistic attributes to sHSPs and point to a critical significance of the NT-IXI motif in αB-crystallin assembly, polydispersity, and chaperone activity.

Suggested Citation

  • Russell McFarland & Rozhan Noroozi & Adam P. Miller & Steve L. Reichow, 2024. "Dynamic fibrillar assembly of αB-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54647-7
    DOI: 10.1038/s41467-024-54647-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54647-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54647-7?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. Moritz Mühlhofer & Carsten Peters & Thomas Kriehuber & Marina Kreuzeder & Pamina Kazman & Natalia Rodina & Bernd Reif & Martin Haslbeck & Sevil Weinkauf & Johannes Buchner, 2021. "Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Kyeong Kyu Kim & Rosalind Kim & Sung-Hou Kim, 1998. "Crystal structure of a small heat-shock protein," Nature, Nature, vol. 394(6693), pages 595-599, 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. Moritz Mühlhofer & Carsten Peters & Thomas Kriehuber & Marina Kreuzeder & Pamina Kazman & Natalia Rodina & Bernd Reif & Martin Haslbeck & Sevil Weinkauf & Johannes Buchner, 2021. "Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble," Nature Communications, Nature, vol. 12(1), pages 1-14, 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:15:y:2024:i:1:d:10.1038_s41467-024-54647-7. 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.