Structural determinants of the PDE6 GAF A domain for binding the inhibitory γ-subunit and noncatalytic cGMP

Abstract

AbstractPhotoreceptor cGMP phosphodiesterases (PDE6 family) are modular enzymes with each catalytic subunit containing two N-terminal regulatory GAF domains, GAF A and GAF B. The GAF A domains contribute to dimerization of the PDE6 catalytic subunits and to binding of the inhibitory Pγ subunits, and represent candidate sites for noncatalytic binding of cGMP. We performed a mutational analysis of selected residues from the GAF A domain of cone PDEα′ to identify the cGMP-binding pocket and delineate the Pγ-binding surface. Results of this analysis establish the noncatalytic cGMP-binding site within the PDE6 GAF A domain and suggest that occupation of the pocket by cGMP is required for high-affinity binding of Pγ to the proximate contact surface