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Ultrafast structural changes direct the first molecular events of vision
Thomas Gruhl1, Tobias Weinert1, Matthew J Rodrigues1
1Division of Biology and Chemistry, Laboratory for Biomolecular Research, Paul Scherrer Institute, Villigen PSI, Switzerland.
Nature
|March 23, 2023
Summary
Researchers used ultrafast crystallography to reveal how light energy stored in retinal drives the initial protein changes necessary for vision. This explains the earliest steps in visual signal transduction and G protein-coupled receptor activation.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biophysics
Background:
- Vision begins with rhodopsin, a light-sensitive G protein-coupled receptor (GPCR).
- Photon absorption by 11-cis retinal triggers its isomerization to all-trans retinal, initiating visual signal transduction.
- The precise mechanism of how photoactivated retinal induces conformational changes in rhodopsin is not fully understood.
Purpose of the Study:
- To elucidate the intramolecular mechanism by which photoactivated retinal initiates conformational changes in rhodopsin.
- To understand how the energy from photon absorption is stored and released to activate the protein.
- To investigate the early structural dynamics of rhodopsin following photoactivation.
Main Methods:
- Ultrafast time-resolved crystallography at room temperature.
- Analysis of structural changes in rhodopsin at picosecond timescales after photoactivation.
Main Results:
- At 1 picosecond post-photoactivation, the isomerized retinal distorts and detaches from its binding pocket interactions.
- Excess photon energy is released via anisotropic protein "breathing" motions towards the extracellular space.
- Early protein side-chain motions occur in regions critical for later G protein-coupled receptor activation.
Conclusions:
- The study reveals how the energy of absorbed photons is stored in a distorted retinal and released to initiate protein conformational changes.
- Early structural dynamics provide insights into the fundamental molecular mechanisms of vision and GPCR activation.
- Findings illuminate the initial steps of vertebrate vision and the broader class A GPCR activation pathway.
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