A Systems Chemoproteomic Analysis of Acyl-CoA/Protein Interaction Networks

Area of Science:

• Biochemistry
• Proteomics
• Systems Biology

Background:

• Acyl-coenzyme A (CoA) interactions with proteins are vital but poorly understood globally.
• The scope and selectivity of these interactions remain largely undefined.
• Understanding these interactions is crucial for deciphering metabolic roles in health and disease.

Purpose of the Study:

• To introduce CATNIP (CoA/AcetylTraNsferase Interaction Profiling), a novel chemoproteomic platform.
• To enable high-throughput analysis of acyl-CoA/protein interactions in endogenous proteomes.
• To profile acyl-CoA selectivity and identify protein interaction networks.

Main Methods:

• Development and application of the CATNIP chemoproteomic platform.
• Utilizing competitive dose-response data and unbiased clustering for protein identification.
• Employing systems-level analyses for network assessment and proteomic annotation.

Main Results:

• Identification of acetyl-CoA binding proteins using CATNIP.
• Profiling of acyl-CoA/protein interaction selectivity, revealing specific engagement signatures.
• Discovery of a non-enzymatic acylation site in NAT10, likely due to acyl-CoA binding.

Conclusions:

• CATNIP provides a powerful tool for high-throughput analysis of acyl-CoA/protein interactions.
• The study elucidates acyl-CoA selectivity and identifies key binding proteins.
• Integration of chemoproteomics and systems biology advances understanding of acyl-CoA metabolism.