研究発表

The membrane-proximal C-terminal region (Pro-C) is important for the regulation of G-protein coupled receptors, but the Pro-C binding to a cytosolic regulator has not been structurally analyzed. The chemokine receptors CCR2/5 bind to the cytosolic regulator FROUNT. The structures of CCR2 Pro-C bound with FROUNT or biomembrane-mimicking micelles were determined by NMR. Cross-saturation-based experiments revealed that the binding surface on Pro-C for FROUNT overlapped with the binding site for membrane, suggesting competitive binding of Pro-C between FROUNT and membrane. These results support an equilibrium model: chemokine binding changes the conformational equilibrium of CCR2/5 toward the active state, and Pro-C switches its binding partner from the membrane to FROUNT.