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

Authors
  • Yang, Xiaoyun1
  • Ma, Yinliang1
  • Li, Yimiao1
  • Dong, Yating1
  • Yu, Lily L2
  • Wang, Hong1
  • Guo, Lulin1
  • Wu, Chen3
  • Yu, Xiaochun4
  • Liu, Xiuhua5
  • 1 College of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, Hebei, PR China. , (China)
  • 2 Westridge School, 324 Madeline Dr., Pasadena, CA, 91105, USA.
  • 3 College of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, Hebei, PR China. Electronic address: [email protected] , (China)
  • 4 Life Science Institute, Westlake University, Hangzhou, Zhejiang, PR China. Electronic address: [email protected]n. , (China)
  • 5 College of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, Hebei, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
DNA repair
Publication Date
Oct 01, 2020
Volume
94
Pages
102899–102899
Identifiers
DOI: 10.1016/j.dnarep.2020.102899
PMID: 32683309
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

MacroD1 is an enzyme that hydrolyzes protein mono-ADP-ribosylation. However, the key catalytic residues of MacroD1 in these biochemical reactions remain elusive. Here, we present the crystal structure of MacroD1 in a complex with ADP-ribose (ADPR). The β5-α10-loop functions as a switch loop to mediate substrate recognition and right orientation. The conserved Phe272 in the β5-α10-loop plays a crucial role in the orientation of ADPR distal ribose, and a conserved hydrogen-bond network contributes significantly to hold and orient the catalytic water12, which mediates ADPR hydrolysis. Moreover, we found that MacroD1 was recruited to the sites of DNA damage via recognition of ADP-ribosylation at DNA lesions. The MacroD1-mediated ADPR hydrolysis is essential for DNA damage repair. Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair. Copyright © 2020 Elsevier B.V. All rights reserved.

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