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

Autor:	Sabbarini IM; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Reif D; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., McQuown AJ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Nelliat AR; Graduate Program in Systems Biology, Harvard Medical School, Boston, MA 02115, USA., Prince J; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Membreno BS; RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Wu CC; RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Murray AW; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Denic V; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: vdenic@mcb.harvard.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2023 Jan 19; Vol. 83 (2), pp. 252-265.e13. Date of Electronic Publication: 2023 Jan 10.
DOI:	10.1016/j.molcel.2022.12.012
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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