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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The interplay between metal ion binding and the activity of thiol proteins, particularly within the protein disulfide isomerase family, remains an area of active investigation due to the critical role that these proteins play in many vital processes. This research investigates the interaction between recombinant human PDIA1 and zinc ions, focusing on the subsequent implications for PDIA1’s conformational stability and enzymatic activity. Employing isothermal titration calorimetry and differential scanning calorimetry, we systematically compared the zinc binding capabilities of both oxidized and reduced forms of PDIA1 and assessed the structural consequences of this interaction. Our results demonstrate that PDIA1 can bind zinc both in reduced and oxidized states, but with significantly different stoichiometry and more pronounced conformational effects in the reduced form of PDIA1. Furthermore, zinc binding was observed to inhibit the catalytic activity of reduced-PDIA1, likely due to induced alterations in its conformation. These findings unveil a potential regulatory mechanism in PDIA1, wherein metal ion binding under reductive conditions modulates its activity. Our study highlights the potential role of zinc in regulating the catalytic function of PDIA1 through conformational modulation, suggesting a nuanced interplay between metal binding and protein stability in the broader context of cellular redox regulation.

Details

Title
Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase
Author
Ana Iochabel Soares Moretti 1   VIAFID ORCID Logo  ; Baksheeva, Viktoria E 2 ; Andrei Yu Roman 2 ; Tiphany Coralie De Bessa 1   VIAFID ORCID Logo  ; Devred, François 2   VIAFID ORCID Logo  ; Kovacic, Hervé 2   VIAFID ORCID Logo  ; Tsvetkov, Philipp O 2   VIAFID ORCID Logo 

 Vascular Biology Laboratory (LIM64), School of Medicine, Heart Institute (InCor), Cardiopneumology Department, University of São Paulo, Campus Sao Paulo, Sao Paulo 05403-000, Brazil 
 Aix Marseille Univ, CNRS, UMR 7051, INP, Inst Neurophysiopathol, Fac Sciences Médicales et Paramédicales, 13005 Marseille, France[email protected] (F.D.); [email protected] (H.K.) 
First page
2095
Publication year
2024
Publication date
2024
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2930971280
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.