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Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation

Xiaoyun Yang1, Yinliang Ma1, Yimiao Li1

  • 1College of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, Hebei, PR China.

DNA Repair
|July 20, 2020
PubMed

Insights

MacroD1 enzyme activity in DNA repair is revealed. Structural insights show how MacroD1 hydrolyzes ADP-ribosylation, essential for repairing DNA damage.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • MacroD1 is an enzyme catalyzing protein mono-ADP-ribosylation hydrolysis.
  • The precise catalytic residues and mechanism of MacroD1 remain unclear.

Purpose of the Study:

  • To elucidate the structural basis of MacroD1's catalytic activity.
  • To investigate MacroD1's role in DNA damage repair.

Main Methods:

  • X-ray crystallography of MacroD1 in complex with ADP-ribose (ADPR).
  • Biochemical assays to assess enzyme function and substrate interaction.

Main Results:

  • The crystal structure reveals the β5-α10-loop acts as a switch for substrate recognition.
  • Conserved residue Phe272 and a hydrogen-bond network are critical for ADPR hydrolysis.
  • MacroD1 is recruited to DNA damage sites and facilitates DNA repair through ADPR hydrolysis.

Conclusions:

  • MacroD1's structure provides insights into its ADP-ribosylation hydrolysis mechanism.
  • MacroD1 plays a vital role in DNA damage repair by hydrolyzing ADP-ribosylation marks.
Keywords:
ADP-ribosylationADPRCrystal structureDNA damage repairMacroD1

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