title: Domain organization and conformational plasticity of the G protein effector, PDE6.
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.
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
authors: Zhixian
authors: Z
authors: Zhang
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
authors: Feng
authors: F
authors: He
authors: Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, Utah 84132.
authors: Ryan
authors: R
authors: Constantine
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
authors: Matthew L
authors: ML
authors: Baker
authors: Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, Utah 84132.
authors: Wolfgang
authors: W
authors: Baehr
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
authors: Michael F
authors: MF
authors: Schmid
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and twensel@bcm.edu.
authors: Theodore G
authors: TG
authors: Wensel
authors: From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
authors: Melina A
authors: MA
authors: Agosto
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry*; D002417:Cattle; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000737:chemistry*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007140:Immunoglobulin Fab Fragments; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6
keywords: conformational change; cryo-electron microscopy; phosphodiesterases; phototransduction; retina; tertiary structure