AI Article Synopsis
- Post-translational modifications like farnesylation and geranylgeranylation at cysteine residues are crucial for the function and localization of over 100 proteins, including significant ones involved in cancer and infections.
- The study introduces new isoprenoid analogues, YnF and YnGG, allowing for advanced profiling of prenylated proteins in live cells through quantitative chemical proteomics.
- A total of 80 prenylated proteins were identified, with 64 discovered for the first time at their natural levels, showcasing the ability to analyze prenylation dynamics and its implications in diseases such as choroideremia.
Article Abstract
Post-translational farnesylation or geranylgeranylation at a C-terminal cysteine residue regulates the localization and function of over 100 proteins, including the Ras isoforms, and is a therapeutic target in diseases including cancer and infection. Here, we report global and selective profiling of prenylated proteins in living cells enabled by the development of isoprenoid analogues YnF and YnGG in combination with quantitative chemical proteomics. Eighty prenylated proteins were identified in a single human cell line, 64 for the first time at endogenous abundance without metabolic perturbation. We further demonstrate that YnF and YnGG enable direct identification of post-translationally processed prenylated peptides, proteome-wide quantitative analysis of prenylation dynamics and alternative prenylation in response to four different prenyltransferase inhibitors, and quantification of defective Rab prenylation in a model of the retinal degenerative disease choroideremia.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544531 | PMC |
| http://dx.doi.org/10.1038/s41557-019-0237-6 | DOI Listing |
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