A Zpr1 co-chaperone mediates folding of eukaryotic translation elongation factor 1A via a GTPase cycle.

Autor:	McQuown AJ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Nelliat AR; 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., Sabbarini IM; 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., 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 Sep 07; Vol. 83 (17), pp. 3108-3122.e13. Date of Electronic Publication: 2023 Aug 18.
DOI:	10.1016/j.molcel.2023.07.028
Abstrakt:	General protein folding is mediated by chaperones that utilize ATP hydrolysis to regulate client binding and release. Zinc-finger protein 1 (Zpr1) is an essential ATP-independent chaperone dedicated to the biogenesis of eukaryotic translation elongation factor 1A (eEF1A), a highly abundant GTP-binding protein. How Zpr1-mediated folding is regulated to ensure rapid Zpr1 recycling remains an unanswered question. Here, we use yeast genetics and microscopy analysis, biochemical reconstitution, and structural modeling to reveal that folding of eEF1A by Zpr1 requires GTP hydrolysis. Furthermore, we identify the highly conserved altered inheritance of mitochondria 29 (Aim29) protein as a Zpr1 co-chaperone that recognizes eEF1A in the GTP-bound, pre-hydrolysis conformation. This interaction dampens Zpr1⋅eEF1A GTPase activity and facilitates client exit from the folding cycle. Our work reveals that a bespoke ATP-independent chaperone system has mechanistic similarity to ATPase chaperones but unexpectedly relies on client GTP hydrolysis to regulate the chaperone-client interaction. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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