SignatureFinder enables sequence mining to identify cobalamin-dependent photoreceptor proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Photoreceptors typically sense blue or red light, mediating cellular responses.
• The discovery of cobalamin-dependent photoreceptor CarH extended light sensing to green wavelengths.
• Identifying new green light photoreceptors is challenging due to poor database annotations of cobalamin-binding domains (CBDs).

Purpose of the Study:

• To develop a computational method for identifying novel light-responsive CBD-containing proteins.
• To expand the known repertoire of green-light photoreceptors.
• To provide a tool for broader applications in identifying proteins with specific biological ligand interactions.

Main Methods:

• Developed SignatureFinder, a computational workflow combining sequence and structural analyses.
• Utilized SignatureFinder to mine a database of 128,000 CBD-containing sequences.
• Experimentally confirmed the light responsiveness of identified proteins.
• Determined the crystal structure of a novel CBD domain.

Main Results:

• Identified diverse, previously unknown CBD-containing photoreceptors.
• Confirmed the light-sensing capabilities of newly identified proteins.
• Elucidated the structural basis of light interaction with the cobalamin chromophore via signature elements.
• Significantly expanded the family of known green-light photoreceptors.

Conclusions:

• SignatureFinder is an effective tool for discovering novel light-responsive proteins.
• The study expands the known diversity of cobalamin-dependent photoreceptors, particularly those sensing green light.
• The findings provide insights into the molecular mechanisms of photoreception and offer a versatile web server for future research.