In:
The EMBO Journal, EMBO, Vol. 34, No. 20 ( 2015-10-14), p. 2506-2521
Kurzfassung:
image Three dimensional structures of the E3 ubiquitin ligase parkin in its auto‐inhibited, optimized and activated forms show how its ubiquitin‐like domain (Ubl) is the key controller of enzyme function, being allosterically displaced through phospho‐ubiquitin recruitment to unveil a masked E2~Ub binding pocket required for full ubiquitination activity. The Ubl domain keeps parkin kept inactive in the absence of phosphorylation signals. A hinge in the centre of parkin optimizes a phospho‐ubiquitin binding patch at the RING 0‐ RING 1 interface. Phospho‐ubiquitin binding along a unique helix in the RING 1 domain releases the inhibitory Ubl domain. Ubl domain displacement reveals a ubiquitin‐binding surface that enhances E2~Ub engagement. Structural details show how parkin function can be altered by mutations in early‐onset Parkinson's disease.
Materialart:
Online-Ressource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.201592337
Sprache:
Englisch
Verlag:
EMBO
Publikationsdatum:
2015
ZDB Id:
1467419-1
ZDB Id:
586044-1
SSG:
12