7KZH

Zinc finger antiviral protein (ZAP) central domain

Summary for 7KZH

• Entry DOI: 10.2210/pdb7kzh/pdb
• Descriptor: Zinc finger CCCH-type antiviral protein 1, ZINC ION (3 entities in total)
• Functional Keywords: restriction factor, antiviral protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 23686.30

Authors

Pornillos, O.P. (deposition date: 2020-12-10, release date: 2021-12-15, Last modification date: 2024-10-16)

Primary citation

Xue, G.,Braczyk, K.,Goncalves-Carneiro, D.,Dawidziak, D.M.,Sanchez, K.,Ong, H.,Wan, Y.,Zadrozny, K.K.,Ganser-Pornillos, B.K.,Bieniasz, P.D.,Pornillos, O.
Poly(ADP-ribose) potentiates ZAP antiviral activity.
Plos Pathog., 18:e1009202-e1009202, 2022

PubMed Abstract: 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.

PubMed: 35130321
DOI: 10.1371/journal.ppat.1009202

Experimental method

X-RAY DIFFRACTION (2.49 Å)