Structural basis for gene regulation by a B12-dependent photoreceptor

Area of Science:

• Structural Biology
• Molecular Biology
• Biochemistry

Background:

• Photoreceptor proteins are crucial for light sensing and response in organisms.
• CarH-type photoreceptors utilize adenosylcobalamin, a vitamin B12 derivative, as a light-sensing chromophore.
• These photoreceptors mediate light-dependent gene regulation.

Purpose of the Study:

• To elucidate the structural mechanisms underlying CarH-mediated light-dependent gene regulation.
• To visualize the conformational changes of CarH in response to light and DNA binding.

Main Methods:

• X-ray crystallography was employed to determine the structures of Thermus thermophilus CarH.
• Structures were obtained for CarH in the dark (free and DNA-bound) and light-exposed states.

Main Results:

• Crystal structures reveal adenosylcobalamin mediates CarH tetramer formation in the dark, repressing transcription via binding to the promoter -35 element.
• Light exposure induces large-scale conformational changes in CarH, leading to transcriptional activation.
• CarH assembly involves the functional repurposing of two independent protein modules.

Conclusions:

• Adenosylcobalamin is functionally repurposed from an enzyme cofactor to a light sensor in CarH.
• The study reveals a novel mechanism of light-dependent gene regulation.
• These findings expand the known biological roles of vitamin B12.