Poly(ADP-ribose) potentiates ZAP antiviral activity.

Autor: Xue G; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Braczyk K; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Gonçalves-Carneiro D; Laboratory of Retrovirology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America., Dawidziak DM; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Sanchez K; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Ong H; Laboratory of Retrovirology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America., Wan Y; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Zadrozny KK; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Ganser-Pornillos BK; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America., Bieniasz PD; Laboratory of Retrovirology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America., Pornillos O; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Feb 07; Vol. 18 (2), pp. e1009202. Date of Electronic Publication: 2022 Feb 07 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1009202
Abstrakt: Zinc-finger antiviral protein (ZAP), also known as poly(ADP-ribose) polymerase 13 (PARP13), is an antiviral factor that selectively targets viral RNA for degradation. ZAP is active against both DNA and RNA viruses, including important human pathogens such as hepatitis B virus and type 1 human immunodeficiency virus (HIV-1). ZAP selectively binds CpG dinucleotides through its N-terminal RNA-binding domain, which consists of four zinc fingers. ZAP also contains a central region that consists of a fifth zinc finger and two WWE domains. Through structural and biochemical studies, we found that the fifth zinc finger and tandem WWEs of ZAP combine into a single integrated domain that binds to poly(ADP-ribose) (PAR), a cellular polynucleotide. PAR binding is mediated by the second WWE module of ZAP and likely involves specific recognition of an adenosine diphosphate-containing unit of PAR. Mutation of the PAR binding site in ZAP abrogates the interaction in vitro and diminishes ZAP activity against a CpG-rich HIV-1 reporter virus and murine leukemia virus. In cells, PAR facilitates formation of non-membranous sub-cellular compartments such as DNA repair foci, spindle poles and cytosolic RNA stress granules. Our results suggest that ZAP-mediated viral mRNA degradation is facilitated by PAR, and provides a biophysical rationale for the reported association of ZAP with RNA stress granules.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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