Moran Shalev-Benami

Prof. Moran Shalev-Benami,  Associate Professor at Weizmann Institute of Science’s Department of Chemical and Structural Biology, published Structural and dynamic insights into agonist recognition and function of the thromboxane A2 receptor in the February issue of Nature Communications. Together with her research team, Prof. Shalev Benami determined the structure of the thromboxane A2 receptor (TP), a key protein involved in blood clotting and muscle contraction. The findings clarify how the receptor is activated and how molecules access its binding site within the cell membrane. These molecular-level insights can support the development of improved therapeutics for clotting disorders and cardiovascular diseases associated with TP.

Abstract:
The thromboxane A₂ receptor (TP), expressed in platelets and smooth muscle, plays an important role in blood clotting and muscle contraction. The endogenous ligand of this G protein-coupled receptor (GPCR), thromboxane A₂ (TXA₂), is a short-lived arachidonic acid metabolite with a half-life of ∼30 seconds, which makes investigating the TP structure and activation mechanism highly challenging. Here we determine the structures of the TP in complex with the synthetic agonists, U46619 and I-BOP, stable analogues of the natural ligand, in the presence of the signalling protein partner, G_q. The structures reveal a unique activation switch for the receptor that differs from typical class A GPCR family members.