Format

Send to

Choose Destination
Cell Chem Biol. 2019 Dec 5. pii: S2451-9456(19)30393-9. doi: 10.1016/j.chembiol.2019.11.011. [Epub ahead of print]

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

Author information

1
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
2
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
3
Laboratory of Proteomics and Analytical Technologies, Leidos, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
4
RNA Epitranscriptomics & Proteomics Resource, University of Albany, 1400 Washington Avenue, Albany, NY 12222, USA.
5
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
6
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Electronic address: jordan.meier@nih.gov.

Abstract

Acyl-coenzyme A (CoA)/protein interactions are essential for life. Despite this importance, their global scope and selectivity remains undefined. Here, we describe 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 the selectivity of acyl-CoA/protein interactions, leading to the identification of specific acyl-CoA engagement signatures. Finally, we apply systems-level analyses to assess the features of protein networks that may interact with acyl-CoAs, and use a strategy for high-confidence proteomic annotation of acetyl-CoA-binding proteins to identify a site of non-enzymatic acylation in the NAT10 acetyltransferase domain that is likely driven by acyl-CoA binding. Overall, our studies illustrate how chemoproteomics and systems biology can be integrated to understand the roles of acyl-CoA metabolism in biology and disease.

KEYWORDS:

acetyl-CoA; acetylation; acetyltransferase; activity-based protein profiling; chemical proteomics; epigenetics; malonylation; metabolism; pharmacology; systems biology

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center