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An Effector Site That Stimulates G-protein GTPase in Photoreceptors
Journal article   Open access   Peer reviewed

An Effector Site That Stimulates G-protein GTPase in Photoreceptors

Vladlen Z Slepak, Nikolai O Artemyev, Yun Zhu, Charles L Dumke, Leah Sabacan, John Sondek, Heidi E Hamm, M. Deric Bownds and Vadim Y Arshavsky
The Journal of biological chemistry, Vol.270(24), pp.14319-14324
06/16/1995
DOI: 10.1074/jbc.270.24.14319
PMID: 7782290
url
https://doi.org/10.1074/jbc.270.24.14319View
Published (Version of record) Open Access

Abstract

Heterotrimeric G-proteins mediate between receptors and effectors, acting as molecular clocks. G-protein interactions with activated receptors catalyze the replacement of GDP bound to the α-subunit with GTP. α-Subunits then modulate the activity of downstream effectors until the bound GTP is hydrolyzed. In several signal transduction pathways, including the cGMP cascade of photoreceptor cells, the relatively slow GTPase activity of heterotrimeric G-proteins can be significantly accelerated when they are complexed with corresponding effectors. In the phototransduction cascade the GTPase activity of photoreceptor G-protein, transducin, is substantially accelerated in a complex with its effector, cGMP phosphodiesterase. Here we characterize the stimulation of transducin GTPase by a set of 23 mutant phosphodiesterase γ-subunits (PDEγ) containing single alanine substitutions within a stretch of the 25 C-terminal amino acid residues known to be primarily responsible for the GTPase regulation. The substitution of tryptophan at position 70 completely abolished the acceleration of GTP hydrolysis by transducin in a complex with this mutant. This mutation also resulted in a reduction of PDEγ affinity for transducin, but did not affect PDEγ interactions with the phosphodiesterase catalytic subunits. Single substitutions of 7 other hydrophobic amino acids resulted in a 50-70% reduction in the ability of PDEγ to stimulate transducin GTPase, while substitutions of charged and polar amino acids had little or no effect. These observations suggest that the role of PDEγ in activation of the transducin GTPase rate may be based on multiple hydrophobic interactions between these molecules.

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