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PDBsum entry 4xkl
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Protein binding/metal binding protein
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PDB id
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4xkl
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References listed in PDB file
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Key reference
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Title
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Molecular basis of ubiquitin recognition by the autophagy receptor calcoco2.
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Authors
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X.Xie,
F.Li,
Y.Wang,
Y.Wang,
Z.Lin,
X.Cheng,
J.Liu,
C.Chen,
L.Pan.
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Ref.
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Autophagy, 2015,
11,
1775-1789.
[DOI no: ]
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PubMed id
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Abstract
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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.
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