Molecular basis of ubiquitin recognition by the autophagy receptor CALCOCO2

Xingqiao Xie1, Faxiang Li1,2, Yuanyuan Wang3

  • 1a State Key Laboratory of Bioorganic and Natural Products Chemistry.

Autophagy
|October 29, 2015
PubMed

Insights

The autophagy receptor CALCOCO2 recognizes ubiquitin-coated pathogens via its C2H2-type zinc finger. This mechanism is crucial for innate immunity and clearing infections.

Area of Science:

  • Cell Biology
  • Immunology
  • Structural Biology

Background:

  • The autophagy receptor CALCOCO2 (also known as NDP52) is vital for innate immunity.
  • It targets ubiquitin-coated pathogens for degradation through selective autophagy.
  • The precise mechanism of how CALCOCO2 recognizes ubiquitinated pathogens remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which CALCOCO2 recognizes ubiquitinated pathogens.
  • To determine the structural basis for this specific recognition.

Main Methods:

  • Biochemical analyses
  • Structural analyses (X-ray crystallography)
  • Ubiquitin-binding assays

Main Results:

  • CALCOCO2's cargo-binding region features a dynamic unconventional zinc finger and a C2H2-type zinc finger.
  • The C2H2-type zinc finger specifically recognizes mono-ubiquitin and poly-ubiquitin chains.
  • The crystal structure revealed a novel zinc finger-ubiquitin binding mode.

Conclusions:

  • CALCOCO2 utilizes its C2H2-type zinc finger for specific recognition of ubiquitinated pathogens.
  • This provides mechanistic insight into CALCOCO2's role in selective autophagy and innate immune defense against infection.

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