Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase

Autor(es)

Moretti, Ana Iochabel Soares ; Baksheeva, Viktoria E. ; Roman, Andrei Yu. ; De Bessa, Tiphany Coralie ; Devred, Francois ; Kovacic, Herve ; Tsvetkov, Philipp O.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 4, p. 15-pg., 2024-02-01.

Resumo

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)

• Processo FAPESP: 11/50469-0 - Interacao entre dissulfeto isomera interacao entre dissulfeto isomerase proteica, rhogdie gtpases da familia rho e ras:identificacao de complexos proteicos.
• Beneficiário: Ana Iochabel Soares Moretti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/23657-8 - Estudo funcional da interação entre a proteína disulfeto isomerase (PDI) e a proteína ligante de actina, Profilina 1
• Beneficiário: Ana Iochabel Soares Moretti
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 09/54764-6 - Regulação da homeostase redox e resposta integrada a estresse pela dissulfeto isomerase protéica (PDI): mecanismos e papel na fisiopatologia e terapêutica de doenças vasculares
• Beneficiário: Francisco Rafael Martins Laurindo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/02070-6 - Mecanismos associados à perda da regulação da Nox1 NADPH oxidase pela dissulfeto isomerase proteica em células com ativação sustentada da via Ras
• Beneficiário: Tiphany Coralie de Bessa
• Modalidade de apoio: Bolsas no Brasil - Doutorado