Integrated structural dynamics uncover a new B₁₂ photoreceptor activation mode

Area of Science:

• Biochemistry
• Photobiology
• Structural Biology

Background:

• Photoreceptor proteins, including those using vitamin B12 derivatives, regulate vital biological processes.
• The precise molecular mechanisms of B12 photoreception and its distinction from thermal pathways are not fully understood.

Purpose of the Study:

• To elucidate the photoactivation mechanism of the B12 photoreceptor CarH from nanoseconds to seconds.
• To understand how light sensing via B12 differs from thermal activation pathways in enzymes.

Main Methods:

• Time-resolved and temperature-resolved structural and spectroscopic methods.
• Quantum chemical calculations.
• Analysis of crystal structures of dark and light-activated states.

Main Results:

• Detailed description of CarH photoactivation, revealing photocleavage of a cobalt-carbon bond in adenosylcobalamin.
• Identification of a novel intermediate adduct linking the adenosyl moiety to the cobalt ion.
• Demonstration that this adduct mediates structural changes and tetramer dissociation, differentiating it from thermal pathways.

Conclusions:

• The study provides a spatiotemporal understanding of CarH photoactivation, highlighting a unique intermediate adduct.
• This mechanism bridges photochemical and photobiological timescales, offering insights into B12-dependent photoreceptor function.
• Findings pave the way for designing novel B12-based photoreceptors for optogenetics.