Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6
Heterotrimeric G proteins communicate signals from activated G protein-coupled receptors to downstream effector proteins. In the phototransduction pathway responsible for vertebrate vision, the G protein-effector complex is comprised of the GTP-bound transducin subunit (GT{middle dot}GTP) and the cyclic GMP (cGMP) phosphodiesterase 6 (PDE6), which stimulates cGMP hydrolysis to transmit signals to the optic nerve. Here we report a cryo-electron microscopy (cryoEM) structure of PDE6 complexed to GTP-bound GT. The structure reveals two GT{middle dot}GTP subunits engaging the PDE6 hetero-tetramer at both the PDE6 catalytic core and the PDE{gamma} subunits, driving extensive rearrangements to relieve all inhibitory constraints on enzyme catalysis. Analysis of the conformational ensemble in the cryoEM data highlights the dynamic nature of the contacts between the two GT{middle dot}GTP subunits and PDE6 that support an alternating-site catalytic mechanism.