5UEF

RNA primer-template complex with guanosine dinucleotide p(5')G(3')p(5')G ligand

5UEF の概要

• エントリーDOI: 10.2210/pdb5uef/pdb
• 関連するPDBエントリー: 5UED 5UEE 5UEG
• 分子名称: RNA (5'-R(*(LCC)P*(LCC)P*(LCC)P*GP*AP*CP*UP*UP*AP*AP*GP*UP*CP*G)-3'), RNA (5'-R(P*GP*G)-3') (3 entities in total)
• 機能のキーワード: rna, dinucleotide
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 10292.50

構造登録者

Zhang, W.,Tam, C.P.,Szostak, J.W. (登録日: 2017-01-02, 公開日: 2017-07-05, 最終更新日: 2023-10-04)

主引用文献

Zhang, W.,Tam, C.P.,Walton, T.,Fahrenbach, A.C.,Birrane, G.,Szostak, J.W.
Insight into the mechanism of nonenzymatic RNA primer extension from the structure of an RNA-GpppG complex.
Proc. Natl. Acad. Sci. U.S.A., 114:7659-7664, 2017

PubMed Abstract: The nonenzymatic copying of RNA templates with imidazole-activated nucleotides is a well-studied model for the emergence of RNA self-replication during the origin of life. We have recently discovered that this reaction can proceed through the formation of an imidazolium-bridged dinucleotide intermediate that reacts rapidly with the primer. To gain insight into the relationship between the structure of this intermediate and its reactivity, we cocrystallized an RNA primer-template complex with a close analog of the intermediate, the triphosphate-bridged guanosine dinucleotide GpppG, and solved a high-resolution X-ray structure of the complex. The structure shows that GpppG binds the RNA template through two Watson-Crick base pairs, with the primer 3'-hydroxyl oriented to attack the 5'-phosphate of the adjacent G residue. Thus, the GpppG structure suggests that the bound imidazolium-bridged dinucleotide intermediate would be preorganized to react with the primer by in-line S2 substitution. The structures of bound GppG and GppppG suggest that the length and flexibility of the 5'-5' linkage are important for optimal preorganization of the complex, whereas the position of the 5'-phosphate of bound pGpG explains the slow rate of oligonucleotide ligation reactions. Our studies provide a structural interpretation for the observed reactivity of the imidazolium-bridged dinucleotide intermediate in nonenzymatic RNA primer extension.

PubMed: 28673998
DOI: 10.1073/pnas.1704006114

実験手法

X-RAY DIFFRACTION (2.1 Å)