The Solution Structure of the Zalpha Domain of the Human RNA Editing Enzyme ADAR1 Reveals a Prepositioned Binding Surface for Z-DNA

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Oct 27

PMID 10535945

Citations 38

Authors

M Schade

C J Turner

R Kuhne

P Schmieder

K Lowenhaupt

A Herbert

A Rich

H Oschkinat

Affiliations

Soon will be listed here.

Abstract

Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zalpha. Here we report the solution structure of free Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.

Citing Articles

ADAR Family Proteins: A Structural Review.

Ashley C, Broni E, Miller 3rd W Curr Issues Mol Biol. 2024; 46(5):3919-3945.

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The role of ADAR1 through and beyond its editing activity in cancer.

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Z-Form Adoption of Nucleic Acid is a Multi-Step Process Which Proceeds through a Melted Intermediate.

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Over-expression of ADAR1 in mice does not initiate or accelerate cancer formation .

Ruiz S, Chalk A, Goradia A, Heraud-Farlow J, Walkley C NAR Cancer. 2023; 5(2):zcad023.

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Differential Structural Features of Two Mutant ADAR1p150 Zα Domains Associated with Aicardi-Goutières Syndrome.

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