Kinetic mechanism of RGS9-1 potentiation by R9AP

Biochemistry. 2006 Sep 5;45(35):10690-7. doi: 10.1021/bi060376a.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Binding Sites
  • Catalysis
  • Cattle
  • Enzyme Activation
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / pharmacokinetics
  • GTP-Binding Proteins / chemistry
  • Kinetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Protein Binding
  • Protein Interaction Mapping
  • RGS Proteins / chemistry*
  • Rod Cell Outer Segment / metabolism*
  • Salts / chemistry
  • Signal Transduction
  • Solutions / chemistry
  • Structure-Activity Relationship

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • RGS Proteins
  • RGS9BP protein, human
  • Salts
  • Solutions
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • transducin GTP phosphohydrolase