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 composed of the GTP-bound transducin alpha subunit (G alpha(T)center dot GTP) and the cyclic GMP (cGMP) phosphodiesterase 6 (PDE6), which stimulates cGMP hydrolysis, leading to hyperpolarization of the photore- ceptor cell. Here we report a cryo-electron microscopy (cryoEM) structure of PDE6 complexed to GTP-bound G alpha(T)center dot G. The structure reveals two GCCT 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 G alpha(T)center dot GTP subunits and PDE6 that supports an alternating-site catalytic mechanism.