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Phosducin induces a structural change in transducin beta gamma
1Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, IL 60612-7334, USA.
Structure (London, England : 1993)
|September 18, 1998
Summary
Phosducin binding to Gt beta gamma subunits changes their conformation, sequestering them from membranes and inhibiting G protein signaling. This structural switch regulates signal transduction cascades.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Phosducin binds Gt beta gamma subunits of transducin, inhibiting the G-protein cycle.
- Phosducin-like proteins regulate diverse heterotrimeric G-protein signaling pathways.
Purpose of the Study:
- To elucidate the structural mechanism by which phosducin regulates Gt beta gamma subunits.
Main Methods:
- X-ray crystallography of a bovine retinal phosducin-Gt beta gamma complex at 2.8 A resolution.
Main Results:
- The crystal structure reveals phosducin domains covering Gt beta gamma, inducing a conformational change.
- A cavity forms between beta-propeller blades 6 and 7 of Gt beta gamma, accommodating the gamma subunit's farnesyl moiety.
Conclusions:
- Gt beta gamma subunits exist in relaxed (R) and tense (T) states, regulated by phosducin.
- Phosducin binding induces the T state, burying the farnesyl group, sequestering Gt beta gamma to the cytosol, and inhibiting signal transduction.
- This phosducin-mediated switch may be a general mechanism for attenuating G protein-coupled signaling.