Zn 2+ -dependent functional switching of ERp18, an ER-resident thioredoxin-like protein.

Autor: Tsutsumi C; Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan., Uegaki K; Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA., Yamashita R; Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan., Ushioda R; Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto 603-8555, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan. Electronic address: ryo3ussy3@cc.kyoto-su.ac.jp., Nagata K; Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto 603-8555, Japan; JT Biohistory Research Hall, Murasaki Town 1-1, Takatsuki City, Osaka 569-1125, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan. Electronic address: nagata@cc.kyoto-su.ac.jp.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2024 Feb 27; Vol. 43 (2), pp. 113682. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1016/j.celrep.2024.113682
Abstrakt: ERp18 is an endoplasmic reticulum (ER)-resident thioredoxin (Trx) family protein, similar to cytosolic Trx1. The Trx-like domain occupies a major portion of the whole ERp18 structure, which is postulated to be an ER paralog of cytosolic Trx1. Here, we elucidate that zinc ion (Zn 2+ ) binds ERp18 through its catalytic motif, triggering oligomerization of ERp18 from a monomer to a trimer. While the monomeric ERp18 has disulfide oxidoreductase activity, the trimeric ERp18 acquires scavenger activity for hydrogen peroxide (H 2 O 2 ) in the ER. Depletion of ERp18 thus causes the accumulation of H 2 O 2 , which is produced during the oxidative folding of nascent polypeptides in the ER. ERp18 knockdown in C. elegans without Prx4 and GPx7/8, both of which are also known to have H 2 O 2 scavenging activity in the ER, shortened the lifespan, suggesting that ERp18 may form a primitive and essential H 2 O 2 scavenging system for the maintenance of redox homeostasis in the ER.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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