1YVU

Crystal structure of A. aeolicus Argonaute

1YVU の概要

• エントリーDOI: 10.2210/pdb1yvu/pdb
• 分子名称: hypothetical protein aq_1447, CALCIUM ION (3 entities in total)
• 機能のキーワード: rnase h fold, rna binding protein, gene regulation
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 83585.83

構造登録者

Yuan, Y.R.,Pei, Y.,Ma, J.B.,Kuryavyi, V.,Zhadina, M.,Meister, G.,Chen, H.Y.,Dauter, Z.,Tuschl, T.,Patel, D.J. (登録日: 2005-02-16, 公開日: 2005-08-09, 最終更新日: 2024-11-20)

主引用文献

Yuan, Y.R.,Pei, Y.,Ma, J.B.,Kuryavyi, V.,Zhadina, M.,Meister, G.,Chen, H.Y.,Dauter, Z.,Tuschl, T.,Patel, D.J.
Crystal structure of A. aeolicus Argonaute provides unique perspectives into the mechanism of guide strand-mediated mRNA cleavage
Mol.Cell, 19:405-419, 2005

PubMed Abstract: Argonaute (Ago) proteins constitute a key component of the RNA-induced silencing complex (RISC). We report the crystal structure of Aquifex aeolicus Ago (Aa-Ago) together with binding and cleavage studies, which establish this eubacterial Ago as a bona fide guide DNA strand-mediated site-specific RNA endonuclease. We have generated a stereochemically robust model of the complex, where the guide DNA-mRNA duplex is positioned within a basic channel spanning the bilobal interface, such that the 5' phosphate of the guide strand can be anchored in a basic pocket, and the mRNA can be positioned for site-specific cleavage by RNase H-type divalent cation-coordinated catalytic Asp residues of the PIWI domain. Domain swap experiments involving chimeras of human Ago (hAgo1) and cleavage-competent hAgo2 reinforce the role of the PIWI domain in "slicer" activity. We propose a four-step Ago-mediated catalytic cleavage cycle model, which provides distinct perspectives into the mechanism of guide strand-mediated mRNA cleavage within the RISC.

PubMed: 16061186
DOI: 10.1016/j.molcel.2005.07.011

実験手法

X-RAY DIFFRACTION (2.9 Å)