Dataset
LanCLs have C-glutathionylation activity with potential to trap the eliminylome
- Documentation:
- Enzyme-mediated damage repair or containment, whilst common for nucleic acids, is rare for proteins. Examples of protein damage are elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenic and aging processes. Bacterial LanC enzymes use Dha/Dhb to form intramolecular C–S linkages, but the functions of their LanC-like (LanCL) counterparts in eukarya are unknown. We show that LanCLs catalyze intermolecular addition of glutathione (GSH) to Dha/Dhb in proteins, driving irreversible protein C-glutathionylation. In vitro chemo-enzymatic methods were developed to site-selectively incorporate Dha/Dhb at phospho-regulated sites in kinases. Strikingly, in archetypal human MAPK-MEK1 such ‘elimination damage’ generated activated kinases (>20% full activation). This unexpected damage-mediated activation was deactivated by LanCL-mediated C-glutathionylation. Surveys of eliminated proteins (the eliminylome) suggest damage by phosphate elimination as a potential source of non-dynamic disregulation of kinase activity. LanCLs can remove these reactive electrophilic structures (the eliminylome), and their potentially deleterious or disregulatory effects, from the proteome.
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Authors
+ Engineering and Physical Sciences Research Council
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- Funder identifier:
- http://dx.doi.org/10.13039/501100000266
- Funding agency for:
- Zeng, Y
- Grant:
- 515587 DI DI STF RESEARCHER FF
- Programme:
- Science 2: Catalysis at the Water-Energy Nexus
- Publisher:
- University of Oxford
- Publication date:
- 2020
- DOI:
- Language:
-
English
- Keywords:
- Subjects:
- Deposit date:
-
2020-12-22
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- Copyright date:
- 2020
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