7TGQ

Zinc finger antiviral protein (ZAP) central domain bound to ADP-ribose

7TGQ の概要

• エントリーDOI: 10.2210/pdb7tgq/pdb
• 関連するPDBエントリー: 7KZH
• 分子名称: Zinc finger CCCH-type antiviral protein 1, ZINC ION, ADENOSINE-5-DIPHOSPHORIBOSE, ... (5 entities in total)
• 機能のキーワード: restriction factor, antiviral protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24129.22

構造登録者

Pornillos, O.P. (登録日: 2022-01-09, 公開日: 2022-02-02, 最終更新日: 2023-10-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)