Abstract
PARP13/ZAP (zinc-finger antiviral protein) acts against multiple viruses by promoting degradation of viral mRNA. PARP13 has four N-terminal zinc (Zn) fingers that bind CG-rich nucleotide sequences, a C-terminal ADP ribosyltransferase fold, and a central region with a fifth Zn finger and tandem WWE domains. The central PARP13 region, ZnF5-WWE1-WWE2, is implicated in binding poly(ADP-ribose); however, there are limited insights into its structure and function. We present crystal structures of ZnF5-WWE1-WWE2 from mouse PARP13 in complex with ADP-ribose and in complex with ATP. The crystal structures and binding studies demonstrate that WWE2 interacts with ADP-ribose and ATP, whereas WWE1 does not have a functional binding site. Binding studies with poly(ADP-ribose) ligands indicate that WWE2 serves as an anchor for preferential binding to the terminal end of poly(ADP-ribose) chains. The composite ZnF5-WWE1-WWE2 structure forms an extended surface to engage ADP-ribose chains, representing a distinctive mode of recognition that provides a framework for investigating the impact of poly(ADP-ribose) on PARP13 function.
Original language | English (US) |
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Article number | 111529 |
Journal | Cell Reports |
Volume | 41 |
Issue number | 4 |
DOIs | |
State | Published - Oct 25 2022 |
Keywords
- ADP-ribose
- ATP
- CP: Molecular biology
- PARP13
- SEC-SAXS
- WWE domain
- X-ray crystallography
- ZAP
- fluorescence polarization
- poly(ADP-ribose)
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology