A chemical reporter facilitates the detection and identification of lysine HMGylation on histones.
Xiucong BaoYing XiongXin LiXiang David LiPublished in: Chemical science (2018)
Lysine 3-hydroxyl-3-methylglutarylation (HMG-K) is a newly identified PTM that can occur non-enzymatically in mitochondria. However, the substrate scope of this new PTM remains insufficiently explored, which has greatly hindered the progress in interpreting its regulatory mechanisms and cellular functions. Here, we report the development of an alkyne-functionalized chemical reporter (HMGAM-yne), for the detection and identification of cellular HMGylated proteins. HMGAM-yne is cell-permeable and metabolically incorporated into proteins in living cells. Subsequent biorthogonal conjugation enables fluorescence visualization and identification of the protein substrates of HMG-K. Using HMGAM-yne, we also identified Sirt5 as an 'eraser' that regulates HMGylation in cells. In addition to the known mitochondrial HMG-K proteins, HMGAM-yne facilitates the discovery of multiple nuclear proteins, including histones, as novel substrates of lysine HMGylation.
Keyphrases
- living cells
- amino acid
- single molecule
- oxidative stress
- fluorescent probe
- crispr cas
- induced apoptosis
- bioinformatics analysis
- small molecule
- cell death
- cell therapy
- transcription factor
- high throughput
- bone marrow
- quantum dots
- ischemia reperfusion injury
- cell proliferation
- endoplasmic reticulum stress
- structural basis
- sensitive detection