In:
The EMBO Journal, EMBO, Vol. 41, No. 20 ( 2022-10-17)
Abstract:
image The ancient ubiquitin‐like protein Urm1 is a sulfur carrier protein for tRNA thiolation, but can also conjugate to target proteins. Here, analysis of the underlying molecular mechanisms reveals that Urm1 attachment simultaneously leads to the persulfidation of cysteines in target proteins, which may protect them from oxidative damage. In vitro ubiquitin‐like conjugation by Urm1 does not require E2 conjugation enzymes or E3 ligases. Urm1 conjugation depends on a peroxidatic cysteine in the target protein and the proximity of lysine, serine or threonine residues. Sulfur transfer from the thiocarboxylated C‐terminus of Urm1 onto cysteines in the target proteins is a mechanistic consequence of the urmylation reaction. High‐resolution crystal structure of an urmylated target protein directly shows formation of an iso‐peptide bond as well as cysteine persulfidation. The Urm1 pathway represents a distinct cysteine persulfidation pathway upon oxidative stress.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2022111318
Language:
English
Publisher:
EMBO
Publication Date:
2022
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12
