ADAR家族蛋白:结构综述

ADAR Family Proteins: A Structural Review.

作者信息

Ashley Carolyn N, Broni Emmanuel, Miller Whelton A

机构信息

Department of Medicine, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA.

Department of Molecular Pharmacology & Neuroscience, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA.

出版信息

Curr Issues Mol Biol. 2024 Apr 26;46(5):3919-3945. doi: 10.3390/cimb46050243.

Abstract

This review aims to highlight the structures of ADAR proteins that have been crucial in the discernment of their functions and are relevant to future therapeutic development. ADAR proteins can correct or diversify genetic information, underscoring their pivotal contribution to protein diversity and the sophistication of neuronal networks. ADAR proteins have numerous functions in RNA editing independent roles and through the mechanisms of A-I RNA editing that continue to be revealed. Provided is a detailed examination of the ADAR family members-ADAR1, ADAR2, and ADAR3-each characterized by distinct isoforms that offer both structural diversity and functional variability, significantly affecting RNA editing mechanisms and exhibiting tissue-specific regulatory patterns, highlighting their shared features, such as double-stranded RNA binding domains (dsRBD) and a catalytic deaminase domain (CDD). Moreover, it explores ADARs' extensive roles in immunity, RNA interference, and disease modulation, demonstrating their ambivalent nature in both the advancement and inhibition of diseases. Through this comprehensive analysis, the review seeks to underline the potential of targeting ADAR proteins in therapeutic strategies, urging continued investigation into their biological mechanisms and health implications.

摘要

本综述旨在突出ADAR蛋白的结构,这些结构对于识别其功能至关重要,且与未来的治疗发展相关。ADAR蛋白可以校正或使遗传信息多样化,这凸显了它们对蛋白质多样性和神经网络复杂性的关键贡献。ADAR蛋白在RNA编辑中具有众多功能,其独立作用以及通过A-I RNA编辑机制发挥的作用仍在不断被揭示。本文对ADAR家族成员——ADAR1、ADAR2和ADAR3进行了详细研究,每个成员都具有独特的亚型,这些亚型既提供了结构多样性,又具有功能变异性,显著影响RNA编辑机制,并表现出组织特异性调控模式,突出了它们的共同特征,如双链RNA结合结构域(dsRBD)和催化脱氨酶结构域(CDD)。此外,还探讨了ADAR蛋白在免疫、RNA干扰和疾病调节中的广泛作用,证明了它们在疾病进展和抑制方面的矛盾性质。通过这种全面分析,本综述旨在强调在治疗策略中靶向ADAR蛋白的潜力,敦促继续研究其生物学机制及其对健康的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c474/11120146/1a0807d20384/cimb-46-00243-g001.jpg

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