Domain Organization and Conformational Plasticity of the G Protein Effector, PDE6 [Protein Structure and Folding]

March 25th, 2015 by Zhang, Z., He, F., Constantine, R., Baker, M. L., Baehr, W., Schmid, M. F., Wensel, T. G., Agosto, M. A.

The cGMP phosphodiesterase of rod photoreceptor cells, PDE6, is the key effector enzyme in phototransduction. Two large catalytic subunits, PDE6α and β, each contain one catalytic domain and two non-catalytic GAF domains, while two small inhibitory PDE6γ subunits allow tight regulation by the G protein transducin. The structure of holo-PDE6 in complex with the ROS-1 antibody Fab fragment was determined by cryo-electron microscopy. The ~11 Ǻ map revealed previously unseen features of PDE6, and each domain was readily fit with high-resolution structures. A structure of PDE6 in complex with prenyl-binding protein (PrBP/δ) indicated the location of the PDE6 C-terminal prenylations. Reconstructions of complexes with Fab fragments bound to N- or C-termini of PDE6γ revealed that PDE6γ stretches from the catalytic domain at one end of the holoenzyme to the GAF-A domain at the other. Removal of PDE6γ caused dramatic structural rearrangements, which were reversed upon its restoration.