A systems chemoproteomic analysis of acyl-CoA signaling networks

Levy, M. J.; Montgomery, D. C.; Sardiu, M. E.; Thorpe, A. L.; Fox, S. D.; Lin, Q.; Andresson, T.; Florens, L.; Washburn, M. P.; Meier, J. L.

doi:10.1101/665281

bioRxiv · 10.1101/665281

A systems chemoproteomic analysis of acyl-CoA signaling networks

Levy, M. J.·Montgomery, D. C.·Sardiu, M. E.·Thorpe, A. L.·Fox, S. D.·Lin, Q.·Andresson, T.·Florens, L.·Washburn, M. P.·Meier, J. L.

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Abstract

Acyl-CoA/protein interactions are required for many functions essential to life including membrane synthesis, oxidative metabolism, and macromolecular acetylation. However, despite their importance, the global scope and selectivity of these protein-metabolite interactions remains undefined. Here we describe the development of CATNIP (CoA/AcetylTraNsferase Interaction Profiling), a chemoproteomic platform for the high-throughput analysis of acyl-CoA/protein interactions in endogenous proteomes. First, we apply CATNIP to identify acetyl-CoA-binding proteins through unbiased clustering of competitive dose-response data. Next, we use this method to profile diverse protein-CoA metabolite interactions, identifying biological processes susceptible to altered acetyl-CoA levels. Finally, we apply systems-level analyses to assess the features of novel protein networks that may interact with acyl-CoAs, and demonstrate a strategy for high-confidence proteomic annotation of acetyl-CoA binding proteins. Overall our studies illustrate the power of integrating chemoproteomics and systems biology, and provide a resource for understanding the roles of acyl-CoA metabolites in biology and disease.

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Levy, M. J., Montgomery, D. C., Sardiu, M. E., Thorpe, A. L., Fox, S. D., Lin, Q., Andresson, T., Florens, L., Washburn, M. P., Meier, J. L.. 2019-06-10. A systems chemoproteomic analysis of acyl-CoA signaling networks. https://doi.org/10.1101/665281

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