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@article{Fedoryshchak:2023:10.1101/2021.12.15.472799,
author = {Fedoryshchak, R and Gorelik, A and Shen, M and Shchepinova, M and Pérez-Dorado, I and Tate, E},
doi = {10.1101/2021.12.15.472799},
journal = {Chemical Science},
pages = {2419--2430},
title = {Discovery of lipid-mediated protein–protein interactions in living cells using metabolic labeling with photoactivatable clickable probes},
url = {http://dx.doi.org/10.1101/2021.12.15.472799},
volume = {14},
year = {2023}
}
TY - JOUR
AB - Protein-protein interactions (PPIs) are essential and pervasive regulatory elements in cell biology. Despite development of a range of techniques to probe PPIs in living systems, there is a dearth of approaches to capture interactions driven by specific post-translational modifications (PTMs). Myristoylation is a lipid PTM added to more than 200 human proteins, where it may regulate membrane localization, stability or activity. Here we report design and synthesis of a panel of novel photocrosslinkable and clickable myristic acid analog probes, and their characterization as efficient substrates for human N -myristoyltransferases NMT1 and NMT2, both biochemically and through X-ray co-crystallography. We demonstrate metabolic incorporation of probes to label NMT substrates in cell culture and in situ intracellular photoactivation to form a covalent crosslink between modified proteins and their interactors, capturing a snapshot of interactions driven by the presence of the lipid PTM. Proteomic analyses revealed both known and multiple novel interactors of a series of myristoylated proteins, including ferroptosis suppressor protein FSP1 and spliceosome-associated RNA helicase DDX46. The concept exemplified by these probes offers an efficient approach for exploring the PTM-specific interactome, which may prove broadly applicable to other PTMs.
AU - Fedoryshchak,R
AU - Gorelik,A
AU - Shen,M
AU - Shchepinova,M
AU - Pérez-Dorado,I
AU - Tate,E
DO - 10.1101/2021.12.15.472799
EP - 2430
PY - 2023///
SN - 2041-6520
SP - 2419
TI - Discovery of lipid-mediated protein–protein interactions in living cells using metabolic labeling with photoactivatable clickable probes
T2 - Chemical Science
UR - http://dx.doi.org/10.1101/2021.12.15.472799
UR - https://pubs.rsc.org/en/content/articlelanding/2023/sc/d2sc06116c
UR - http://hdl.handle.net/10044/1/102098
VL - 14
ER -