Conformational exchange at a C2H2 zinc-binding site facilitates redox sensing by the PML protein.
Structure
; 31(9): 1086-1099.e6, 2023 09 07.
Article
in En
| MEDLINE
| ID: mdl-37473756
ABSTRACT
The promyelocytic leukemia protein, PML, plays a vital role in the cellular response to oxidative stress; however, the molecular mechanism of its action remains poorly understood. Here, we identify redox-sensitive sites of PML. A molecule of PML is cysteine-rich and contains three zinc-binding domains including RING, B-box1, and B-box2. Using in vitro assays, we have compared the sensitivity of the isolated RING and B-box1 domains and shown that B-box1 is more sensitive to oxidation. NMR studies of PML dynamics showed that one of the Zn-coordination sites within the B-box1 undergoes significant conformational exchange, revealing a hotspot for exposure of reactive cysteines. In agreement with the in vitro data, enhancement of the B-box1 Zn-coordination dynamics led to more efficient recruitment of PML into PML nuclear bodies in cells. Overall, our results suggest that the increased sensitivity of B-box1 to oxidative stress makes this domain an important redox-sensing component of PML.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zinc
/
Nuclear Proteins
Language:
En
Journal:
Structure
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos