Structures Of Human Adar2 Bound To Dsrna Reveal Base Flipping Mechanism And Basis For Site Selectivity
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Structures of Human ADAR2 Bound to DsRNA Reveal Base-flipping Mechanism and Basis for Site Selectivity
Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. In this paper, we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. In conclusion, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.
Handbook of Chemical Biology of Nucleic Acids
This handbook is the first to comprehensively cover nucleic acids from fundamentals to recent advances and applications. It is divided into 10 sections where authors present not only basic knowledge but also recent research. Each section consists of extensive review chapters covering the chemistry, biology, and biophysics of nucleic acids as well as their applications in molecular medicine, biotechnology and nanotechnology. All sections within this book are: Physical Chemistry of Nucleic Acids (Section Editor: Prof. Roland Winter), Structural Chemistry of Nucleic Acids (Section Editor: Prof. Janez Plavec), Organic Chemistry of Nucleic Acids (Section Editor: Prof. Piet Herdewijin), Ligand Chemistry of Nucleic Acids (Section Editor: Prof. Marie-Paule Teulade-Fichou), Nucleic Acids and Gene Expression (Section Editor: Prof. Cynthia Burrows), Analytical Methods and Applications of Nucleic Acids (Section Editor: Prof. Chaoyong Yang), Nanotechnology and Nanomaterial Biology of Nucleic Acids (Section Editor: Prof. Zhen Xi), Nucleic Acids Therapeutics (Section Editor: Prof. Katherine Seley-Radtke), Biotechnology and Synthetic Biology of Nucleic Acids (Section Editor: Prof. Eriks Rozners), Functional Nucleic Acids (Section Editor: Prof. Keith R. Fox). The handbook is edited by outstanding leaders with contributions written by international renowned experts. It is a valuable resource not only for researchers but also graduate students working in areas related to nucleic acids who would like to learn more about their important role and potential applications.
Fundamentals of Molecular Structural Biology
Fundamentals of Molecular Structural Biology reviews the mathematical and physical foundations of molecular structural biology. Based on these fundamental concepts, it then describes molecular structure and explains basic genetic mechanisms. Given the increasingly interdisciplinary nature of research, early career researchers and those shifting into an adjacent field often require a "fundamentals" book to get them up-to-speed on the foundations of a particular field. This book fills that niche.