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Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6
Yang Gao1, Gözde Eskici1, Sekar Ramachandran2
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Molecular Cell
|October 2, 2020
Summary
Researchers visualized the structure of a key protein complex in vertebrate vision using cryo-electron microscopy (cryoEM). This reveals how transducin alpha subunits (GαT·GTP) activate cyclic GMP phosphodiesterase 6 (PDE6) for phototransduction.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Neuroscience
Background:
- Heterotrimeric G proteins are crucial signal transducers linking G protein-coupled receptors to effector proteins.
- In vertebrate vision, the G protein transducin (Gt) activates cyclic GMP phosphodiesterase 6 (PDE6) to regulate photoreceptor cell function.
Purpose of the Study:
- To determine the structural basis of PDE6 activation by GTP-bound transducin alpha subunits (GαT·GTP).
- To elucidate the mechanism by which GαT·GTP relieves inhibition and stimulates PDE6 catalytic activity.
Main Methods:
- Cryo-electron microscopy (cryoEM) was employed to capture the structure of the PDE6-GαT·GTP complex.
- Conformational ensemble analysis of the cryoEM data was performed to understand dynamic interactions.
Main Results:
- The cryoEM structure reveals two GαT·GTP subunits binding to the PDE6 hetero-tetramer.
- These interactions occur at both the catalytic core and the PDEγ subunits of PDE6.
- Extensive rearrangements were observed, relieving inhibitory constraints and enabling catalysis.
Conclusions:
- The binding of two GαT·GTP subunits to PDE6 is essential for its activation in phototransduction.
- The dynamic interactions observed support an alternating-site catalytic mechanism for PDE6.
- This structural insight provides a molecular understanding of visual signal processing.
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