Glycoprotein IIbIIIa is a heterodimeric integral membrane complex found on the surface of platelets and endothelial cells. A member of the integrin family of adhesion receptors, it plays an important role in blood clotting and wound healing. The goal of this research is to elucidate the structural and functional domain organization of IIbetaIIIalpha, to determine which parts of each subunit are independently folded and which parts are responsible for the various interactions. This will be accomplished through the preparation of fragments representing various parts of each subunit and examining their thermodynamic properties in comparison to those of the parent proteins through a combination of differential scanning calorimetry and spectroscopic methods. Those parts of each subunit which are involved in subunit interactions will be determined by evaluating the ability of the various fragments from one subunit to associate with the other subunit or its fragments. The interactions with divalent metal ions will be further characterized by measuring the effects of those ions on the stability of isolated domains and fragments. Knowledge of the domain structure of IIbetaIIIalpha will be helpful in understanding the molecular basis of diseases (such as Glanzmann's thrombasthenia) resulting from mutations in the genes coding for this receptor. Such knowledge will also serve as a guide to those who would attempt to use recombinant techniques to map the functions of this protein and other members of the integrin family.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
1R03TW000264-01
Application #
3432702
Study Section
Special Emphasis Panel (SRC (01))
Project Start
1993-09-30
Project End
1996-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
American National Red Cross
Department
Type
DUNS #
003255213
City
Washington
State
DC
Country
United States
Zip Code
20006