Format

Send to

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

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

Author information

1
From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and.
2
Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, Utah 84132.
3
From the Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and twensel@bcm.edu.

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.

KEYWORDS:

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

PMID:
25809480
PMCID:
PMC4432299
DOI:
10.1074/jbc.M115.647636
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center