The Role of the Z-DNA Binding Domain in Innate Immunity and Stress Granules

De Chen Chiang; Yan Li; Siew Kit Ng

doi:10.3389/fimmu.2020.625504

The Role of the Z-DNA Binding Domain in Innate Immunity and Stress Granules

Front Immunol. 2021 Feb 3:11:625504. doi: 10.3389/fimmu.2020.625504. eCollection 2020.

Authors

De Chen Chiang^{1

2}, Yan Li³, Siew Kit Ng^{1

3}

Affiliations

¹ Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia.
² School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia.
³ Department of Biology, Southern University of Science and Technology, Shenzhen, China.

Abstract

Both DNA and RNA can maintain left-handed double helical Z-conformation under physiological condition, but only when stabilized by Z-DNA binding domain (ZDBD). After initial discovery in RNA editing enzyme ADAR1, ZDBD has also been described in pathogen-sensing proteins ZBP1 and PKZ in host, as well as virulence proteins E3L and ORF112 in viruses. The host-virus antagonism immediately highlights the importance of ZDBD in antiviral innate immunity. Furthermore, Z-RNA binding has been shown to be responsible for the localization of these ZDBD-containing proteins to cytoplasmic stress granules that play central role in coordinating cellular response to stresses. This review sought to consolidate current understanding of Z-RNA sensing in innate immunity and implore possible roles of Z-RNA binding within cytoplasmic stress granules.

Keywords: ADAR1; E3L; PKZ; Z-DNA binding domain; Z-RNA; ZBP1; innate immunity; stress granules.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA, Z-Form / immunology*
DNA-Binding Proteins / immunology*
Humans
Immunity, Innate*
Protein Domains
RNA-Binding Proteins / immunology*
Viral Proteins / immunology*

Substances

DNA, Z-Form
DNA-Binding Proteins
RNA-Binding Proteins
Viral Proteins