1. Domain Organization and Conformational Plasticity of the G Protein Effector, PDE6.
- Author
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Zhixian Zhang, Feng He, Constantine, Ryan, Baker, Matthew L., Baehr, Wolfgang, Schmid, Michael F., Wensel, Theodore G., and Agosto, Melina A.
- Subjects
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PHOSPHODIESTERASES , *ENZYMES , *CATALYSIS synthesis , *CRYOELECTRONICS , *PROTEIN analysis - Abstract
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, whereas 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 cryoelectron microscopy. The ~11 Å 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 thatPDE6γ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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