Kinetic Mechanism of RGS9-1 Potentiation by R9AP
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- 作者：Sheila A. Baker ; Kirill A. Martemyanov ; Alexander S. Shavkunov ; Vadim Y. Arshavsky
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：September 5, 2006
- 年：2006
- 卷：45
- 期：35
- 页码：10690 - 10697
- 全文大小：210K
- 年卷期：v.45,no.35(September 5, 2006)
- ISSN：1520-4995
文摘
The duration of the photoreceptor's response to a light stimulus determines the speed at whichan animal adjusts to ever-changing conditions of the visual environment. One critical component whichregulates the photoresponse duration on the molecular level is the complex between the ninth member ofthe regulators of G protein signaling family (RGS9-1) and its partner, type 5 G protein 
-subunit (G5L).RGS9-1·G5L is responsible for the activation of the GTPase activity of the photoreceptor-specific Gprotein, transducin. Importantly, this function of RGS9-1·G5L is regulated by its membrane anchor,R9AP, which drastically potentiates the ability of RGS9-1·G5L to activate transducin GTPase. In thisstudy, we address the kinetic mechanism of R9AP action and find that it consists primarily of a directincrease in the RGS9-1·G5L activity. We further showed that the binding site for RGS9-1·G5L islocated within the N-terminal putative trihelical domain of R9AP, and even though this domain is sufficientfor binding, it takes the entire R9AP molecule to potentiate the activity of RGS9-1·G5L. The mechanismrevealed in this study is different from and complements another well-established mechanism of regulationof RGS9-1·G5L by the effector enzyme, cGMP phosphodiesterase, which is based entirely on theenhancement in the affinity between RGS9-1·G5L and transducin. Together, these mechanisms ensuretimely transducin inactivation in the course of the photoresponse, a requisite for normal vision.
-subunit (G5L).RGS9-1·G5L is responsible for the activation of the GTPase activity of the photoreceptor-specific Gprotein, transducin. Importantly, this function of RGS9-1·G5L is regulated by its membrane anchor,R9AP, which drastically potentiates the ability of RGS9-1·G5L to activate transducin GTPase. In thisstudy, we address the kinetic mechanism of R9AP action and find that it consists primarily of a directincrease in the RGS9-1·G5L activity. We further showed that the binding site for RGS9-1·G5L islocated within the N-terminal putative trihelical domain of R9AP, and even though this domain is sufficientfor binding, it takes the entire R9AP molecule to potentiate the activity of RGS9-1·G5L. The mechanismrevealed in this study is different from and complements another well-established mechanism of regulationof RGS9-1·G5L by the effector enzyme, cGMP phosphodiesterase, which is based entirely on theenhancement in the affinity between RGS9-1·G5L and transducin. Together, these mechanisms ensuretimely transducin inactivation in the course of the photoresponse, a requisite for normal vision.