| Full text | |
| Author(s): |
Moretti, Ana Iochabel Soares
;
Baksheeva, Viktoria E.
;
Roman, Andrei Yu.
;
De Bessa, Tiphany Coralie
;
Devred, Francois
;
Kovacic, Herve
;
Tsvetkov, Philipp O.
Total Authors: 7
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 4, p. 15-pg., 2024-02-01. |
| 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. (AU) | |
| FAPESP's process: | 14/23657-8 - Functional interaction studies between protein disulfide isomerase (PDI), and the actin-binding protein Profilin 1 |
| Grantee: | Ana Iochabel Soares Moretti |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases |
| Grantee: | Francisco Rafael Martins Laurindo |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/02070-6 - Mechanisms associated with loss of regulation of NADPH oxidase Nox1 by protein disulfide isomerase in cells with sustained activation of the Ras pathway |
| Grantee: | Tiphany Coralie de Bessa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |