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

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 media...

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Autores principales: Yang, Xiaoyun, Ma, Yinliang, Li, Yimiao, Dong, Yating, Yu, Lily L., Wang, Hong, Guo, Lulin, Wu, Chen, Yu, Xiaochun, Liu, Xiuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313891/
https://www.ncbi.nlm.nih.gov/pubmed/32683309
http://dx.doi.org/10.1016/j.dnarep.2020.102899
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author Yang, Xiaoyun
Ma, Yinliang
Li, Yimiao
Dong, Yating
Yu, Lily L.
Wang, Hong
Guo, Lulin
Wu, Chen
Yu, Xiaochun
Liu, Xiuhua
author_facet Yang, Xiaoyun
Ma, Yinliang
Li, Yimiao
Dong, Yating
Yu, Lily L.
Wang, Hong
Guo, Lulin
Wu, Chen
Yu, Xiaochun
Liu, Xiuhua
author_sort Yang, Xiaoyun
collection PubMed
description 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 Phe(272) 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.
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spelling pubmed-73138912020-06-24 Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation Yang, Xiaoyun Ma, Yinliang Li, Yimiao Dong, Yating Yu, Lily L. Wang, Hong Guo, Lulin Wu, Chen Yu, Xiaochun Liu, Xiuhua DNA Repair (Amst) Article 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 Phe(272) 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. Elsevier B.V. 2020-10 2020-06-22 /pmc/articles/PMC7313891/ /pubmed/32683309 http://dx.doi.org/10.1016/j.dnarep.2020.102899 Text en © 2020 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Yang, Xiaoyun
Ma, Yinliang
Li, Yimiao
Dong, Yating
Yu, Lily L.
Wang, Hong
Guo, Lulin
Wu, Chen
Yu, Xiaochun
Liu, Xiuhua
Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title_full Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title_fullStr Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title_full_unstemmed Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title_short Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation
title_sort molecular basis for the macrod1-mediated hydrolysis of adp-ribosylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313891/
https://www.ncbi.nlm.nih.gov/pubmed/32683309
http://dx.doi.org/10.1016/j.dnarep.2020.102899
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