Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases.
Mol Cell
; 47(6): 933-42, 2012 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-22885007
ABSTRACT
Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanism by which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformational biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/U-box E3E2~Ub ligase complex and identify the long sought-after source of allostery for RING/U-Box activation of E2~Ub conjugates.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina
/
Enzimas de Conjugação de Ubiquitina
/
Ubiquitina-Proteína Ligases
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article