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

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.

journal_name

Cell Chem Biol

journal_title

Cell chemical biology

authors

Levy MJ,Montgomery DC,Sardiu ME,Montano JL,Bergholtz SE,Nance KD,Thorpe AL,Fox SD,Lin Q,Andresson T,Florens L,Washburn MP,Meier JL

doi

10.1016/j.chembiol.2019.11.011

subject

Has Abstract

pub_date

2020-03-19 00:00:00

pages

322-333.e5

issue

3

eissn

2451-9456

issn

2451-9448

pii

S2451-9456(19)30393-9

journal_volume

27

pub_type

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