[en] Z-nucleic acid structures play vital roles in cellular processes and have implications in innate immunity due to their recognition by Zα domains containing proteins (Z-DNA/Z-RNA binding proteins, ZBPs). Although Zα domains have been identified in six proteins, including viral E3L, ORF112, and I73R, as well as, cellular ADAR1, ZBP1, and PKZ, their prevalence across living organisms remains largely unexplored. In this study, we introduce a computational approach to predict Zα domains, leading to the revelation of previously unidentified Zα domain-containing proteins in eukaryotic organisms, including non-metazoan species. Our findings encompass the discovery of new ZBPs in previously unexplored giant viruses, members of the Nucleocytoviricota phylum. Through experimental validation, we confirm the Zα functionality of select proteins, establishing their capability to induce the B-to-Z conversion. Additionally, we identify Zα-like domains within bacterial proteins. While these domains share certain features with Zα domains, they lack the ability to bind to Z-nucleic acids or facilitate the B-to-Z DNA conversion. Our findings significantly expand the ZBP family across a wide spectrum of organisms and raise intriguing questions about the evolutionary origins of Zα-containing proteins. Moreover, our study offers fresh perspectives on the functional significance of Zα domains in virus sensing and innate immunity and opens avenues for exploring hitherto undiscovered functions of ZBPs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Romero, Miguel F ; DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, California, USA
Krall, Jeffrey B ; Department of Biochemistry and Molecular Genetics, University of Colorado at Denver, Aurora, Colorado, USA
Nichols, Parker J ; Department of Biochemistry and Molecular Genetics, University of Colorado at Denver, Aurora, Colorado, USA
Vantreeck, Jillian ; Department of Biochemistry and Molecular Genetics, University of Colorado at Denver, Aurora, Colorado, USA
Henen, Morkos A; Department of Biochemistry and Molecular Genetics, University of Colorado at Denver, Aurora, Colorado, USA
Dejardin, Emmanuel ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Molecular Immunology and Signal Transduction
Schulz, Frederik ; DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, California, USA. Electronic address: fschulz@lbl.gov
Vicens, Quentin ; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA. Electronic address: qvicens@central.uh.edu
Vögeli, Beat ; Department of Biochemistry and Molecular Genetics, University of Colorado at Denver, Aurora, Colorado, USA. Electronic address: beat.vogeli@cuanschutz.edu
Diallo, Mamadou Amadou ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Novel Z-DNA binding domains in giant viruses.
Publication date :
August 2024
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology Inc., United States
The work conducted by the U.S. Department of Energy Joint Genome Institute ( https://ror.org/04xm1d337 ), a DOE Office of Science User Facility, is supported by the Office of Science of the U.S. Department of Energy operated under Contract No. DE-AC02-05CH11231.We gratefully acknowledge the National Science Foundation (Award #2153787 to Q.V. and B.V.), and the National Institutes of Health (Award #1F31AI167396 to P.N.).
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