Journal article
Phosphodiesterase 6B, cGMP-specific rod beta: Basis Sequence: Mouse
AfCS-Nature Molecule Pages, Vol.2008
02/27/2008
DOI: 10.1038/mp.a001755.01
Abstract
PDE6B is a catalytic subunit of the rod-specific cyclic nucleotide phosphodiesterase 6 (PDE6) enzyme. Rod PDE6 is a heterotetramer composed of two catalytic subunits, PDE6A and PDE6B, and two identical inhibitory PDE6G subunits. In rod photoreceptors, PDE6 is located in the specialized ciliary compartments called outer segments (OS), where it associates with disc membranes. The membrane attachment of PDE6 is secured by farnesylation of the PDE6A C terminus and geranylgeranylation of the PDE6B C terminus. PDE6B contains two regulatory N-terminal GAF domains named for their presence in cGMP-regulated PDEs, adenylyl cyclases, and the E. coli protein Fh1A. A highly conserved catalytic domain is present in the C-terminal part of the molecule. The GAFa domain of PDE6B apparently serves as a site for noncatalytic binding of cyclic guanosine monophosphate (cGMP). Noncatalytic binding of cGMP is thought to modulate the affinity of the PDE6A and PDE6B interaction with PDE6G. PDE6 is highly selective for cGMP over cyclic AMP and hydrolyzes cGMP with the Km value of 10-20 μM. PDE6 serves as an effector enzyme in the rod phototransduction cascade. In the dark, the catalytic activity of PDE6, which is blocked by PDE6G, is very low. Light-induced activation of PDE6 results from the displacement of the PDE6G subunits from the catalytic sites on PDE6A and PDE6B by the GTP-bound transducin-α molecules. The catalytic efficiency of the fully activated PDE6 with cGMP as a substrate (kcat/Km ratio is approximately 3x108 M-1s-1) approaches the diffusion limit. PDE6 is re-inhibited by PDE6G when transducin-α hydrolyzes bound GTP in the reaction controlled by the RGS9 (regulator of G-protein signaling 9) GAP (GTPase accelerating protein) complex. Mutations in PDE6B can lead to autosomal recessive retinitis pigmentosa, a common hereditary retinal degeneration leading to vision loss caused by the death of the rod and cone photoreceptors.
Details
- Title: Subtitle
- Phosphodiesterase 6B, cGMP-specific rod beta: Basis Sequence: Mouse
- Creators
- Nikolai O Artemyev
- Resource Type
- Journal article
- Publication Details
- AfCS-Nature Molecule Pages, Vol.2008
- DOI
- 10.1038/mp.a001755.01
- ISSN
- 1477-5921
- eISSN
- 1477-5921
- Language
- English
- Date published
- 02/27/2008
- Academic Unit
- Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984025564802771
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