Domain organization and conformational plasticity of the G protein effector, PDE6

J Biol Chem. 2015 May 15;290(20):12833-43. doi: 10.1074/jbc.M115.647636. Epub 2015 Mar 25.


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.

Keywords: conformational change; cryo-electron microscopy; phosphodiesterases; phototransduction; retina; tertiary structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / chemistry*
  • Cattle
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / chemistry*
  • Humans
  • Immunoglobulin Fab Fragments / chemistry*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary


  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin Fab Fragments
  • Cyclic Nucleotide Phosphodiesterases, Type 6

Associated data

  • PDB/12E8
  • PDB/1FQJ
  • PDB/1KSH
  • PDB/1T9S
  • PDB/3DBA
  • PDB/3IBJ
  • PDB/3JWR