Zα and Zβ domains of ADAR1 and ZBP1 bind G-quadruplexes with nanomolar affinities, establishing Zβ as a G-quadruplex-specific domain
Year: 2026
Type: article
Abstract: While it is well established that the Zα domains of ADAR1 and ZBP1 proteins bind Z-form-prone nucleic acids (Z-NAs), it has also been shown that the Zα domain of ADAR1 binds DNA G-quadruplexes (GQs). However, no binding partner of the structurally homologous Zβ domain of ADAR1 has been identified to date. Based on AlphaFold and molecular dynamics simulations, it has recently been suggested that Zβ of ADAR1 targets its substrate by recognizing GQs. Here, we provide the first experimental evidence for Zβ binding to select GQ RNA and DNA in vitro, with structural specificity and nanomolar affinity. We also demonstrate that the Zα domains of ZBP1 and ADAR1 bind to both DNA and RNA GQs with similar affinity. These findings extend the range of potential functional roles for these proteins and open new hypotheses for testing in cells.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkag419
Institutions: University of Colorado Anschutz, InsideOutBio (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Awards: G1565180698, G2708376974, G3298087253, 600 MHz NMR console and cold probe, G3433089422, G5029337574, Structural characterization of the mechanism leading to recognition of Alu elements by the Z-RNA-binding domain of ADAR1, G9000232728, Functional protein disorder in intracellular transport, G9001225491
OpenAlex ID: W7160091196