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Zinc-finger protein Zpr1 is a bespoke chaperone essential for eEF1A biogenesis

  1. Author:
    Sabbarini, Ibrahim M
    Reif, Dvir
    McQuown, Alexander J
    Nelliat, Anjali R
    Prince, Jeffrey
    Santiago Membreno,Britnie
    Wu,Colin
    Murray, Andrew W
    Denic, Vladimir

  2. Author Address

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Graduate Program in Systems Biology, Harvard Medical School, Boston, MA 02115, USA., RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: vdenic@mcb.harvard.edu.,
    1. Year: 2023
    2. Date: Jan 19
    3. Epub Date: 2023 01 04
  2. Journal: Molecular Cell
    1. 83
    2. 2
    3. Pages: 252-265
  4. Type of Article: Article
  1. Abstract:

    The conserved regulon of heat shock factor 1 in budding yeast contains chaperones for general protein folding as well as zinc-finger protein Zpr1, whose essential role in archaea and eukaryotes remains unknown. Here, we show that Zpr1 depletion causes acute proteotoxicity driven by biosynthesis of misfolded eukaryotic translation elongation factor 1A (eEF1A). Prolonged Zpr1 depletion leads to eEF1A insufficiency, thereby inducing the integrated stress response and inhibiting protein synthesis. Strikingly, we show by using two distinct biochemical reconstitution approaches that Zpr1 enables eEF1A to achieve a conformational state resistant to protease digestion. Lastly, we use a ColabFold model of the Zpr1-eEF1A complex to reveal a folding mechanism mediated by the Zpr1's zinc-finger and alpha-helical hairpin structures. Our work uncovers the long-sought-after function of Zpr1 as a bespoke chaperone tailored to the biogenesis of one of the most abundant proteins in the cell. Copyright © 2022 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.molcel.2022.12.012
  3. PMID: 36630955
  4. View record in Web of Science®
  5. WOS: 000924586200001
  6. PII : S1097-2765(22)01169-8

Library Notes

  1. Fiscal Year: FY2022-2023
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