Conformation change in platelet integrins using surface enhanced Raman microscopy

ANYL 464

Robert J. Forster, robert.forster@dcu.ie1, Tia Keyes2, Uju Inya-Agha2, Agnieszka Michota-Kame2, Niamh Moran3, and Dermot Kenny3. (1) National Center for Sensor Research, Dublin City University, Glasnevin, Dublin 9, Ireland, (2) School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland, (3) Clinical Research Centre and Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland
Thrombosis involves the clotting of blood within an artery or a vein. Gp2b3a is a membrane bound platelet integrin protein that is central to the clotting process. Ex vivo its activity can be modulated by agonists such as Mn(II), EDTA and dithiothreitol (DTT) triggering a conformation change to an activated form that binds fibrinogen. Despite insights from cryo-EM and scanning probe microscopy, the details of the bimolecular mechanisms for the activation of Gp2b3a and its dynamics remain poorly understood. We report on the development of protein compatible nanostructured SERS substrates and SERS insights into the activation mechanism at the molecular level, the physical location of the “pivot” point in switch blade activation and the dynamics of activation. Significantly, SERS indicates that the extent of activation is not the same for every agonist.
 

Analytical Approaches
1:30 PM-4:30 PM, Thursday, August 23, 2007 BCEC -- 104A, Oral

Division of Analytical Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007