The stability and function of human cochaperone Hsp40/DNAJA1 are affected by zinc removal and partially restored by copper

Author(s)

de Jesus, Jemmyson R. ; Linhares, Leonardo A. ; Araga, Annelize Z. B. ; Arruda, Marco A. Z. ; Ramos, Carlos H. I.

• Document type: Journal article
• Source: Biochimie; v. 213, p. 7-pg., 2023-05-30.

Abstract

The imbalance in metal homeostasis can be associated with several human diseases, and exposure to increasing concentrations of metals promotes cell stress and toxicity. Therefore, understanding the cytotoxic effect of metal imbalance is important to unravel the biochemical mechanism of homeostasis and the action of potential protective proteins against metal toxicity. Several studies, including gene deletion in yeast, provide evidence indicating the possible indirect involvement of cochaperones from the Hsp40/DNAJA family in metal homeostasis, possibly through modulating the activity of Hsp 70.This work first investigated the effect of zinc and copper on the conformation and function of the human Hsp40 cochaperone DNAJA1, a zinc-binding protein. DNAJA1 was capable to complement the phenotype of a yeast strain deleted of the ydj1 gene, which was more sensitive to the presence of zinc and copper than the wild-type strain. To gain further insight about the role of the DNAJA family in metal binding, the recombinant human DNAJA1 protein was studied. Zinc removal from DNAJA1 affected both its stability and ability to act as a chaperone, i.e., to protect other proteins from aggregation. The reintroduction of zinc restored the native properties of DNAJA1 and, surprisingly, the addition of copper partially restored the native properties.& COPY; 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/24445-8 - EMU granted in process 2018/25207-0: inductively coupled plasma mass spectrometer
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/00768-0 - Correlation between metals and protein homeostasis: initial studies investigating the incorporation of the 68Zn isotope into the Hsp40 co-chaperone and its effect on yeast
• Grantee: Jemmyson Romário de Jesus
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/25207-0 - Nanometallomics applied to soybean cultivation for studying the effects of metal-related nanoparticles
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/08543-7 - A speciomic toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Regular Research Grants