Kinetic mechanism of RGS9-1 potentiation by R9AP

Sheila A Baker; Kirill A Martemyanov; Alexander S Shavkunov; Vadim Y Arshavsky

doi:10.1021/bi060376a

Back

Kinetic mechanism of RGS9-1 potentiation by R9AP

Journal article

Peer reviewed

Kinetic mechanism of RGS9-1 potentiation by R9AP

Sheila A Baker, Kirill A Martemyanov, Alexander S Shavkunov and Vadim Y Arshavsky

Biochemistry (Easton), Vol.45(35), pp.10690-10697

09/05/2006

DOI: 10.1021/bi060376a

PMID: 16939221

View Online

Abstract

The duration of the photoreceptor's response to a light stimulus determines the speed at which an animal adjusts to ever-changing conditions of the visual environment. One critical component which regulates the photoresponse duration on the molecular level is the complex between the ninth member of the regulators of G protein signaling family (RGS9-1) and its partner, type 5 G protein beta-subunit (Gbeta5L). RGS9-1.Gbeta5L is responsible for the activation of the GTPase activity of the photoreceptor-specific G protein, transducin. Importantly, this function of RGS9-1.Gbeta5L is regulated by its membrane anchor, R9AP, which drastically potentiates the ability of RGS9-1.Gbeta5L to activate transducin GTPase. In this study, we address the kinetic mechanism of R9AP action and find that it consists primarily of a direct increase in the RGS9-1.Gbeta5L activity. We further showed that the binding site for RGS9-1.Gbeta5L is located within the N-terminal putative trihelical domain of R9AP, and even though this domain is sufficient for binding, it takes the entire R9AP molecule to potentiate the activity of RGS9-1.Gbeta5L. The mechanism revealed in this study is different from and complements another well-established mechanism of regulation of RGS9-1.Gbeta5L by the effector enzyme, cGMP phosphodiesterase, which is based entirely on the enhancement in the affinity between RGS9-1.Gbeta5L and transducin. Together, these mechanisms ensure timely transducin inactivation in the course of the photoresponse, a requisite for normal vision.

GTP-Binding Proteins - chemistry

Rod Cell Outer Segment - metabolism

Signal Transduction

Membrane Proteins - genetics

Structure-Activity Relationship

GTP Phosphohydrolases - pharmacokinetics

Protein Interaction Mapping

Solutions - chemistry

GTP Phosphohydrolases - chemistry

Salts - chemistry

Adaptor Proteins, Signal Transducing

Animals

Cattle

Membrane Proteins - physiology

RGS Proteins - chemistry

Protein Binding

Catalysis

Enzyme Activation

Kinetics

Binding Sites

Details

Title: Subtitle: Kinetic mechanism of RGS9-1 potentiation by R9AP
Creators: Sheila A Baker - Department of Ophthalmology, Duke University, Durham, North Carolina 27710, USA
Kirill A Martemyanov
Alexander S Shavkunov
Vadim Y Arshavsky
Resource Type: Journal article
Publication Details: Biochemistry (Easton), Vol.45(35), pp.10690-10697
Publisher: United States
DOI: 10.1021/bi060376a
PMID: 16939221
ISSN: 0006-2960
eISSN: 1520-4995
Grant note: EY-14104 / NEI NIH HHS EY-5722 / NEI NIH HHS EY-12859 / NEI NIH HHS
Language: English
Date published: 09/05/2006
Academic Unit: Iowa Neuroscience Institute; Biochemistry and Molecular Biology; University College Courses; Ophthalmology and Visual Sciences
Record Identifier: 9984024408702771

Metrics

14 Record Views

28 Times Cited - Web of Science