Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Regular paperSite-directed mutagenesis of the cGMP phosphodiesterase γ subunit from bovine rod outer segments: Role of separate amino acid residues in the interaction with catalytic subunits and transducin α subunit
References (32)
- et al.
FEBS Lett.
(1987) - et al.
J. Biol. Chem.
(1990) - et al.
FEBS Lett.
(1986) - et al.
J. Biol. Chem.
(1982) - et al.
FEBS Lett.
(1988) - et al.
Anal. Biochem.
(1969) - et al.
J. Biol. Chem.
(1979) Anal. Biochem.
(1976)- et al.
Gene
(1987) - et al.
J. Biol. Chem.
(1990)
J. Biol. Chem.
J. Mol. Biol.
J. Biol. Chem.
J. Biol. Chem.
J. Biol. Chem.
Annu. Rev. Neurosci.
Cited by (22)
Effect of the ILE86TER mutation in the γ subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling
2012, Cellular SignallingCitation Excerpt :In order to study this mechanism in rods in vivo, we have introduced a mutant form of PDE6γ into the mouse genome, in which the last two C-terminal amino acids Ile86 and Ile87 have been deleted. Previous work with reconstituted rod outer segments has indicated that the carboxyl-terminal tail of PDE6γ may influence γ subunit inhibition of PDE6 catalytic activity [6,21,33], and that the carboxyl-terminal Ile86 and Ile87 may play a particularly important role in this inhibition [4–6,12,21,34–36]. Our studies demonstrate for the first time the essential role of the C-terminus of PDE6γ in the regulation of PDE activity in vivo.
Structural requirements of the photoreceptor phosphodiesterase γ-subunit for inhibition of rod PDE6 holoenzyme and for its activation by transducin
2010, Journal of Biological ChemistryCitation Excerpt :The 10-kDa Pγ inhibitory subunit has two major functional domains. The proline-rich and polycationic region (amino acids 18–45; see Fig. 1A) interacts with the GAF domains of the PDE6 catalytic dimer (8–11) and stabilizes noncatalytic cGMP binding to the GAF domains (12). The C-terminal region (broadly defined as amino acids 62–87) interacts with the catalytic domain and blocks the catalytic activity (8, 9, 13–17).
The inhibitory γ subunit of the rod cGMP phosphodiesterase binds the catalytic subunits in an extended linear structure
2006, Journal of Biological ChemistryCitation Excerpt :This is in good agreement with previous observations that the Pγ polycationic and C-terminal regions are the major Pαβ-interacting domains (2, 4, 6, 37). In particular, mutations of Pγ residues Lys29, Lys31, Arg33 (23), Asn74, His75, and Leu78 (25) disrupt Pγ/Pαβ interactions. In our study, however, the double cysteines for mBP derivatization were placed nearby but not at these residues and replaced uncharged hydrophobic residues (such as Phe30, Phe73, and Leu76), so that mBP can still reach and efficiently photoinsert into Pαβ by mimicking the wild type residues.
Asymmetric interaction between rod cyclic GMP phosphodiesterase γ subunits and αβ subunits
2005, Journal of Biological ChemistryCitation Excerpt :It is well established that there are two major regions of Pγ that interact with Pαβ, the C-terminal region that approximately includes the Pγ residues from Cys68 to the very C-terminal residue Ile87, and the central polycationic region spanning the residues from Val21 to Lys45. It has been suggested that the polycationic region enhances overall Pγ affinity to Pαβ by binding to the GAF domain while the C terminus of Pγ binds to the catalytic site of Pαβ thus maintaining the enzyme in an inactivated state (18, 21, 22). Through kinetic measurements of PDE6 activity using synthetic peptides corresponding to various regions in the Pγ molecule, Mou and Cote (9) showed that the Pγ central region mainly accounted for the binding affinity with the Pαβ GAF domains.
Binding of cGMP to GAF domains in amphibian rod photoreceptor cGMP phosphodiesterase (PDE): Identification of GAF domains in PDE αβ subunits and distinct domains in the PDE γ subunit involved in stimulation of cGMP binding to GAF domains
2002, Journal of Biological ChemistryCitation Excerpt :Differences in sequence and functional domains between mammalian and amphibian PDE subunits might be responsible for the discrepancy. However, recent studies of cGMP binding and its regulation (41-44, 55) have been based on the assumption that frog catalytic subunits have non-catalytic sites similar to those found in bovine catalytic subunits (36, 37), and that frog rod Pγ has functional domains similar to those in bovine rod Pγ (9-11). Thus, it was important to identify both these non-catalytic sites in frog Pαβ and the functional domains of frog rod Pγ.
- 1
Present address: Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehorst 76100, Israel.