Avian cryptochrome 4 binds superoxide.

Area of Science:

• Biophysics
• Photochemistry
• Quantum Biology

Background:

• Flavin-binding cryptochromes are blue-light photoreceptors involved in magnetoreception.
• Their photocycle generates radical pairs, with superoxide (O2-) production during re-oxidation.
• Superoxide-containing radical pairs are hypothesized for magnetosensitivity, but require immobilization due to rapid spin relaxation.

Purpose of the Study:

• Investigate superoxide binding to cryptochrome 4 from *C. livia*.
• Understand the mechanism and functional implications of superoxide interaction with cryptochromes.
• Explore the potential role in magnetosensitive biological radical pairs.

Main Methods:

• All-atom molecular dynamics simulations.
• Density-functional theory calculations.
• Analysis of binding sites, dynamics, and rotational diffusion.

Main Results:

• Superoxide transiently binds to cryptochrome 4 in a positively charged region with 5 flexible arginine-centered sites.
• Binding events lasted tens to hundreds of nanoseconds, significantly slowing rotational diffusion (up to 1 ns correlation time).
• Binding sites efficiently scavenge superoxide near the flavin cofactor, suggesting functional relevance.

Conclusions:

• Cryptochrome 4 exhibits specific superoxide binding sites that can immobilize the radical.
• This immobilization may facilitate the function of flavin semiquinone/superoxide radical pairs in magnetoreception.
• Findings provide insights into the molecular mechanisms of cryptochrome-mediated magnetosensitivity.