4XKL

Crystal structure of NDP52 ZF2 in complex with mono-ubiquitin

Summary for 4XKL

• Entry DOI: 10.2210/pdb4xkl/pdb
• Related: 2MXP
• Descriptor: Ubiquitin, Calcium-binding and coiled-coil domain-containing protein 2, GLYCEROL, ... (6 entities in total)
• Functional Keywords: ndp52, ubiquitin, zinc finger, autophagy receptor, complex, protein binding-metal binding protein complex, protein binding/metal binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Ubiquitin: Cytoplasm . 60S ribosomal protein L40: Cytoplasm : P62987; Cytoplasm, perinuclear region : Q13137
• Total number of polymer chains: 4
• Total formula weight: 26076.52

Authors

Xie, X.,Li, F.,Wang, Y.,Lin, Z.,Chen, X.,Liu, J.,Pan, L. (deposition date: 2015-01-12, release date: 2015-11-11, Last modification date: 2024-10-30)

Primary citation

Xie, X.,Li, F.,Wang, Y.,Wang, Y.,Lin, Z.,Cheng, X.,Liu, J.,Chen, C.,Pan, L.
Molecular basis of ubiquitin recognition by the autophagy receptor CALCOCO2
Autophagy, 11:1775-1789, 2015

PubMed Abstract: 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.

PubMed: 26506893
DOI: 10.1080/15548627.2015.1082025

Experimental method

X-RAY DIFFRACTION (2.1 Å)