Functional and structural correlations of individual αIIbβ3 molecules

The divalent cation Mn2+ and the reducing agent dithiothreitol directly shift integrins from their inactive to their active states. We used transmission electron microscopy and laser tweezers-based force spectroscopy to determine whether structural rearrangements induced by these agents in the integrin alphallbbeta3 correlate with its ability to bind fibrinogen. Mn2+ increased the probability of specific fibrinogen-alphallbbeta3 interactions nearly 20-fold in platelets, and both Mn2+ and dithiothreitol increased the probability more tions exclusively involving the distal ends of the stalks. These results indicate that there is a direct correlation between alphallbbeta3 activation and the overall conformation of the molecule. Further, they are consistent with the presence of a linked equilibrium between single inactive and single active alphallbbeta3 molecules and active alphallbbeta3 clusters. (C) 2004 by The American Society of Hematology.