Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.

Redox regulation of cyclophilin a by glutathionylation / P. Ghezzi, S. Casagrande, T. Massignan, M. Basso, E. Bellacchio, L. Mollica, E. Biasini, R. Tonelli, I. Eberini, E. Gianazza, W.W. Dai, M. Fratelli, M. Salmona, B. Sherry, V. Bonetto. - In: PROTEOMICS. - ISSN 1615-9853. - 6:3(2006), pp. 817-825. [10.1002/pmic.200500177]

Redox regulation of cyclophilin a by glutathionylation

L. Mollica;I. Eberini;E. Gianazza;
2006

Abstract

Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.
Settore BIO/10 - Biochimica
Article (author)
File in questo prodotto:
File Dimensione Formato  
pmic.200500177.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 254.4 kB
Formato Adobe PDF
254.4 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/5393
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 39
  • ???jsp.display-item.citation.isi??? 35
social impact