Tokyo Institute of Technology: Conformational Equilibria in GPCRs provides critical clues about activation mechanisms

A multinational research team led by Dr. Adnan Sljoka (RIKEN), Prof. R. Scott Prosser (Univ. of Toronto) with collaborations with Dr. Duy Phuoc Tran and Prof. Akio Kitao (Tokyo Tech) and Prof. Roger K. Sunahara (Univ. of California San Diego) has carried out experimental and computational studies, revealing key steps associated with the activation of the human adenosine A2A receptor (A2AR). A2AR is a member of superfamily of receptors called G protein-coupled receptors (GPCRs) (major drug targets) which engage the G protein and initiates cell signaling. The research team discovered that A2AR is represented by at least two inactive conformations and three active conformations whose populations are dependent on ligands and activation states of G protein, and that communication between receptor and G-protein is important for activation and signalling. This study is expected to allow researchers to reach new level of insight in GPCR activation and disease mechanism.