Activation Mechanism of Jumping Spider Rhodopsin-1 Revealed by Classical Molecular Dynamics

Area of Science:

• Biochemistry
• Structural Biology
• Optogenetics

Background:

• Animal rhodopsins are G-protein-coupled receptors (GPCRs) crucial for vision and light sensing.
• They are classified as monostable or bistable based on chromophore behavior post-photoisomerization.
• Bistable rhodopsins, like Jumping Spider Rhodopsin-1 (JSR1), offer optogenetic advantages due to their photocycle properties.

Purpose of the Study:

• To elucidate the activation mechanism of bistable rhodopsins, specifically JSR1.
• To compare the JSR1 activation mechanism with that of monostable bovine rhodopsin (Rho).
• To provide structural insights into JSR1 for potential optogenetic applications.

Main Methods:

• Classical molecular dynamics (MD) simulations were performed on JSR1 in its dark and active states.
• Hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) calculations were employed.
• Simulations were compared with spectroscopic data and known mechanisms of bovine rhodopsin.

Main Results:

• MD simulations revealed similarities and differences in JSR1 activation compared to bovine rhodopsin.
• QM/MM calculations supported the experimental spectroscopic findings for JSR1.
• The study provides a molecular-level understanding of JSR1's photocycle.

Conclusions:

• JSR1 exhibits a distinct activation mechanism compared to monostable rhodopsins.
• The findings advance the understanding of bistable rhodopsin function and photocycling.
• This research lays the groundwork for JSR1's application in optogenetics.