Bacterial ligases reveal fundamental principles of polyubiquitin specificity.
Mol Cell
; 83(24): 4538-4554.e4, 2023 Dec 21.
Article
en En
| MEDLINE
| ID: mdl-38091999
Homologous to E6AP C terminus (HECT) E3 ubiquitin (Ub) ligases direct substrates toward distinct cellular fates dictated by the specific form of monomeric or polymeric Ub (polyUb) signal attached. How polyUb specificity is achieved has been a long-standing mystery, despite extensive study in various hosts, ranging from yeast to human. The bacterial pathogens enterohemorrhagic Escherichia coli and Salmonella Typhimurium encode outlying examples of "HECT-like" (bHECT) E3 ligases, but commonalities to eukaryotic HECT (eHECT) mechanism and specificity had not been explored. We expanded the bHECT family with examples in human and plant pathogens. Three bHECT structures in primed, Ub-loaded states resolved key details of the entire Ub ligation process. One structure provided a rare glimpse into the act of ligating polyUb, yielding a means to rewire polyUb specificity of both bHECT and eHECT ligases. Studying this evolutionarily distinct bHECT family has revealed insight into the function of key bacterial virulence factors as well as fundamental principles underlying HECT-type Ub ligation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poliubiquitina
/
Ubiquitina-Proteína Ligasas
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos