Discovery of metal-binding proteins by thermal proteome profiling.
Nat Chem Biol
; 20(6): 770-778, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38409364
ABSTRACT
Metal-binding proteins (MBPs) have various and important biological roles in all living species and many human diseases are intricately linked to dysfunctional MBPs. Here, we report a chemoproteomic method named 'metal extraction-triggered agitation logged by thermal proteome profiling' (METAL-TPP) to globally profile MBPs in proteomes. The method involves the extraction of metals from MBPs using chelators and monitoring the resulting protein stability changes through thermal proteome profiling. Applying METAL-TPP to the human proteome with a broad-spectrum chelator, EDTA, revealed a group of proteins with reduced thermal stability that contained both previously known MBPs and currently unannotated MBP candidates. Biochemical characterization of one potential target, glutamine-fructose-6-phosphate transaminase 2 (GFPT2), showed that zinc bound the protein, inhibited its enzymatic activity and modulated the hexosamine biosynthesis pathway. METAL-TPP profiling with another chelator, TPEN, uncovered additional MBPs in proteomes. Collectively, this study developed a robust tool for proteomic discovery of MBPs and provides a rich resource for functional studies of metals in cell biology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteome
/
Proteomics
Limits:
Humans
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2024
Type:
Article
Affiliation country:
China