Journal
AUTOPHAGY
Volume 11, Issue 10, Pages 1775-1789Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1082025
Keywords
autophagy receptor; CALCOCO2; NDP52; selective autophagy; ubiquitin-binding zinc finger; xenophagy; zinc finger; ubiquitin complex
Categories
Funding
- National Natural Science Foundation of China [31470749]
- National Basic Research Program of China [2013CB836900]
- Thousand Talents Program young investigator award
- Shanghai Rising Star Scholar award [13QA1404300]
- State Key Laboratory of Bioorganic and Natural Products Chemistry and Chinese Academy of Sciences
- China Postdoctoral Science Foundation [2014M561538]
Ask authors/readers for more resources
The autophagy receptor CALCOCO2/NDP52 functions as a bridging adaptor and plays an essential role in the selective autophagic degradation of invading pathogens by specifically recognizing ubiquitin-coated intracellular pathogens and subsequently targeting them to the autophagic machinery; thereby it is required for innate immune defense against a range of infectious pathogens in mammals. However, the mechanistic basis underlying CALCOCO2-mediated specific recognition of ubiqutinated pathogens is still unknown. Here, using biochemical and structural analyses, we demonstrated that the cargo-binding region of CALCOCO2 contains a dynamic unconventional zinc finger as well as a C2H2-type zinc-finger, and only the C2H2-type zinc finger specifically recognizes mono-ubiquitin or poly-ubiquitin chains. In addition to elucidating the specific ubiquitin recognition mechanism of CALCOCO2, the structure of the CALCOCO2 C2H2-type zinc finger in complex with mono-ubiquitin also uncovers a unique zinc finger-binding mode for ubiquitin. Our findings provide mechanistic insight into how CALCOCO2 targets ubiquitin-decorated pathogens for autophagic degradations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available