Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction.
Elife
; 62017 03 02.
Article
em En
| MEDLINE
| ID: mdl-28252385
ABSTRACT
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PXIncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5. Mutagenesis of the SNX5-PXIncE binding surface disrupts a previously unsuspected interaction between SNX5 and the cation-independent mannose-6-phosphate receptor (CI-MPR). Addition of IncE peptide inhibits the interaction of CI-MPR with SNX5. Finally, C. trachomatis infection interferes with the SNX5CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5. Our results provide new insights into retromer assembly and underscore the power of using pathogens to discover disease-related cell biology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Chlamydia trachomatis
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Receptor IGF Tipo 2
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Interações Hospedeiro-Patógeno
/
Evasão da Resposta Imune
/
Nexinas de Classificação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos