5JS2

Human Argonaute-2 Bound to a Modified siRNA

5JS2 の概要

• エントリーDOI: 10.2210/pdb5js2/pdb
• 関連するPDBエントリー: 5JS1
• 分子名称: Protein argonaute-2, modified siRNA, PHENOL, ... (6 entities in total)
• 機能のキーワード: argonaute, sirna, rnai, nuclease, hydrolase-rna complex, hydrolase/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, P-body: Q9UKV8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99650.11

構造登録者

Schirle, N.T.,MacRae, I.J. (登録日: 2016-05-07, 公開日: 2016-07-20, 最終更新日: 2023-09-27)

主引用文献

Schirle, N.T.,Kinberger, G.A.,Murray, H.F.,Lima, W.F.,Prakash, T.P.,MacRae, I.J.
Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide.
J.Am.Chem.Soc., 138:8694-8697, 2016

PubMed Abstract: Incorporation of chemical modifications into small interfering RNAs (siRNAs) increases their metabolic stability and improves their tissue distribution. However, how these modifications impact interactions with Argonaute-2 (Ago2), the molecular target of siRNAs, is not known. Herein we present the crystal structure of human Ago2 bound to a metabolically stable siRNA containing extensive backbone modifications. Comparison to the structure of an equivalent unmodified-siRNA complex indicates that the structure of Ago2 is relatively unaffected by chemical modifications in the bound siRNA. In contrast, the modified siRNA appears to be much more plastic and shifts, relative to the unmodified siRNA, to optimize contacts with Ago2. Structure-activity analysis reveals that even major conformational perturbations in the 3' half of the siRNA seed region have a relatively modest effect on knockdown potency. These findings provide an explanation for a variety of modification patterns tolerated in siRNAs and a structural basis for advancing therapeutic siRNA design.

PubMed: 27380263
DOI: 10.1021/jacs.6b04454

実験手法

X-RAY DIFFRACTION (2.954 Å)