NMR Dynamics Study Reveals the Zα Domain of Human ADAR1 Associates with and Dissociates from Z-RNA More Slowly than Z-DNA.
ACS Chem Biol
; 14(2): 245-255, 2019 02 15.
Article
em En
| MEDLINE
| ID: mdl-30592616
ABSTRACT
Human RNA editing enzyme ADAR1 deaminates adenosine in pre-mRNA to yield inosine. The Zα domain of human ADAR1 (hZαADAR1) binds specifically to left-handed Z-RNA as well as Z-DNA and stabilizes the Z-conformation. To answer the question of how hZαADAR1 can induce both the B-Z transition of DNA and the A-Z transition of RNA, we investigated the structure and dynamics of hZαADAR1 in complex with 6-base-pair Z-DNA or Z-RNA. We performed chemical shift perturbation and relaxation dispersion experiments on hZαADAR1 upon binding to Z-DNA as well as Z-RNA. Our study demonstrates the unique dynamics of hZαADAR1 during the A-Z transition of RNA, in which the hZαADAR1 protein forms a thermodynamically stable complex with Z-RNA, similar to Z-DNA, but kinetically converts RNA to the Z-form more slowly than DNA. We also discovered some distinct structural features of hZαADAR1 in the Z-RNA binding conformation. Our results suggest that the A-Z transition of RNA facilitated by hZαADAR1 displays unique structural and dynamic features that may be involved in targeting ADAR1 for a role in recognition of RNA substrates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Adenosina Desaminase
/
Proteínas de Ligação a RNA
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Ressonância Magnética Nuclear Biomolecular
/
DNA Forma Z
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2019
Tipo de documento:
Article