Type

Journal Article

Authors

Sarah O'Neill
Dermot Kenny
Robert J. Forster
Tia E. Keyes
Niamh Moran
Deirdre Leane
Geraldine M Walsh

Subjects

Biochemistry

Topics
platelet glycoprotein gpiib iiia complex platelet activation protein conformation humans nitric oxide protein processing post translational integrins spectrum analysis raman disulfides manganese sulfhydryl compounds nitrogen oxides s nitrosoglutathione animals metabolism

S-Nitrosylation of platelet alphaIIbbeta3 as revealed by Raman spectroscopy. (2007)

Abstract The exact mechanisms regulating conformational changes in the platelet-specific integrin alphaIIbbeta3 are not fully understood. However, a role exists for thiol/disulfide exchange in integrin conformational changes leading to altered disulfide bonding patterns, via its endogenous thiol isomerase activity. Nitric oxide (NO) accelerates this intrinsic enzymatic activity and, in doing so, reverses the activational state of the integrin on the platelet surface toward a more unactivated one. We propose that it is an S-nitrosylation-induced "shuffling" of thiol/disulfide exchange that regulates this reversal of the activated state of the integrin. In this study, we use Raman spectroscopy to explore S-nitrosylation of purified alphaIIbbeta3. Using S-nitrosoglutathione (GSNO) as a model system, we identify Raman markers which show a direct interaction between NO and the thiol groups of the integrin and reveal many of the structural changes that occur in alphaIIbbeta3 in the course of not only its activation but also its deactivation. Key conformational changes are detected within the integrin when treated with manganese (Mn2+), occurring mainly in the cysteine and disulfide regions of the protein, confirming the importance of thiol/disulfide exchange in integrin activation. These changes are subsequently shown to be reversed in the presence of NO.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Sarah O'Neill, Dermot Kenny, Robert J. Forster, Tia E. Keyes, Niamh Moran, Deirdre Leane, Geraldine M Walsh

Experts in our system

1
Dermot Kenny
Royal College of Surgeons in Ireland
 
2
Robert J. Forster
Dublin City University
Total Publications: 92
 
3
Tia E. Keyes
Dublin City University
Total Publications: 104
 
4
Niamh Moran
Royal College of Surgeons in Ireland
Total Publications: 50