| RRC ID |
82644
|
| 著者 |
Chai Q, Wang X, Qiang L, Zhang Y, Ge P, Lu Z, Zhong Y, Li B, Wang J, Zhang L, Zhou D, Li W, Dong W, Pang Y, Gao GF, Liu CH.
|
| タイトル |
A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Ubiquitin-mediated xenophagy, a type of selective autophagy, plays crucial roles in host defense against intracellular pathogens including Mycobacterium tuberculosis (Mtb). However, the exact mechanism by which host ubiquitin targets invaded microbes to trigger xenophagy remains obscure. Here we show that ubiquitin could recognize Mtb surface protein Rv1468c, a previously unidentified ubiquitin-binding protein containing a eukaryotic-like ubiquitin-associated (UBA) domain. The UBA-mediated direct binding of ubiquitin to, but not E3 ubiquitin ligases-mediated ubiquitination of, Rv1468c recruits autophagy receptor p62 to deliver mycobacteria into LC3-associated autophagosomes. Disruption of Rv1468c-ubiquitin interaction attenuates xenophagic clearance of Mtb in macrophages, and increases bacterial loads in mice with elevated inflammatory responses. Together, our findings reveal a unique mechanism of host xenophagy triggered by direct binding of ubiquitin to the pathogen surface protein, and indicate a diplomatic strategy adopted by Mtb to benefit its persistent intracellular infection through controlling intracellular bacterial loads and restricting host inflammatory responses.
|
| 巻・号 |
10(1)
|
| ページ |
1973
|
| 公開日 |
2019-4-29
|
| DOI |
10.1038/s41467-019-09955-8
|
| PII |
10.1038/s41467-019-09955-8
|
| PMID |
31036822
|
| PMC |
PMC6488588
|
| MeSH |
Autophagosomes / metabolism*
Immunity, Innate / physiology
Macrophages / metabolism*
Mycobacterium tuberculosis / metabolism*
RNA, Messenger / metabolism
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases / metabolism
|
| IF |
12.121
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
