Year: 2015
Type: article
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 cryo-electron 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 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.
Source: Journal of Biological Chemistry
Institutions: Baylor College of Medicine, University of Utah
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G159655901, G1688340195, G2590921614, G340396948, Photoreceptor Ciliopathies: UNC119 Paralogs and NPHP10/NPHP5, G4815039349, Resource for Biocomputing, Visualization, and Informatics, 3 D Electron Microscopy of Macromolecules, G794106571, G9000001160, G9000015997, G9000044598, G9000068432, G9000114072, G9000214964
OpenAlex ID: W2073683845