Structural Mimicry by a Bacterial F Box Effector Hijacks the Host Ubiquitin-Proteasome System.
Structure
; 25(2): 376-383, 2017 02 07.
Article
em En
| MEDLINE
| ID: mdl-28111017
ABSTRACT
Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K48-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase. The structure confirms that AnkB contains an N-terminal F box similar to Skp2 and a C-terminal substrate-binding domain similar to eukaryotic ankyrin repeats. We identified crucial amino acids in the substrate-binding domain of AnkB and showed them to be essential for the function of AnkB in L. pneumophila intracellular proliferation. The study reveals how Legionella uses molecular mimicry to manipulate the host ubiquitination pathway and proliferate intracellularly.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Legionella pneumophila
/
Anquirinas
/
Proteínas Periplásmicas
/
Proteínas Quinases Associadas a Fase S
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Interações Hospedeiro-Patógeno
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Structure
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá