NMR Studies of Proteins Involved in Cell Adhesion Processes

Many biological processes on the molecular level are associated with membrane-bound receptors or other integral membrane proteins. We have been working with proteins that are domains of receptors, or inhibit their function. The first topic are the T-cell surface glycoprotein receptor CD2 and its counter receptor CD58. The other topic is about antagonists of the integrin adhesion receptor glycoprotein IIbIIIa (GPIIbIIIa) which is found on platelet surfaces. Human CD2 is a glycoprotein, and the carbohydrate of its adhesion domain is crucial for adhesion function. The platelet receptor GPIIbIIIa, a Ca2+ dependent heterodimeric glycoprotein from the integrin family, binds fibrinogen and mediates the aggregation of platelets to form a blood clot. Natural protein antagonists of this receptor have primarily been found in the venum of various snakes, which have been termed disintegrins, and in the saliva of blood-sucking leeches. They contain an Arg-Gly-Asp (RGD) sequence in their active site. Due to the potent antiplatelet effect of these RGD proteins, the structures of their active sites have been of considerable interest for the design of antithromotic drugs.