3DLB

Crystal structure of the guide-strand-containing Argonaute protein silencing complex

3DLB の概要

• エントリーDOI: 10.2210/pdb3dlb/pdb
• 関連するPDBエントリー: 3DLH
• 分子名称: argonaute, DNA (5'-D(*DTP*DGP*DAP*DGP*DGP*DTP*DAP*DGP*DTP*DA)-3') (3 entities in total)
• 機能のキーワード: argonaute, protein-dna complex, plasmid, nucleic acid binding protein-dna complex, nucleic acid binding protein/dna
• 由来する生物種: Thermus thermophilus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159705.60

構造登録者

Wang, Y.,Sheng, G.,Patel, D.J. (登録日: 2008-06-26, 公開日: 2008-09-02, 最終更新日: 2024-02-21)

主引用文献

Wang, Y.,Sheng, G.,Juranek, S.,Tuschl, T.,Patel, D.J.
Structure of the guide-strand-containing argonaute silencing complex.
Nature, 456:209-213, 2008

PubMed Abstract: The slicer activity of the RNA-induced silencing complex is associated with argonaute, the RNase H-like PIWI domain of which catalyses guide-strand-mediated sequence-specific cleavage of target messenger RNA. Here we report on the crystal structure of Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-base DNA guide strand, thereby identifying the nucleic-acid-binding channel positioned between the PAZ- and PIWI-containing lobes, as well as the pivot-like conformational changes associated with complex formation. The bound guide strand is anchored at both of its ends, with the solvent-exposed Watson-Crick edges of stacked bases 2 to 6 positioned for nucleation with the mRNA target, whereas two critically positioned arginines lock bases 10 and 11 at the cleavage site into an unanticipated orthogonal alignment. Biochemical studies indicate that key amino acid residues at the active site and those lining the 5'-phosphate-binding pocket made up of the Mid domain are critical for cleavage activity, whereas alterations of residues lining the 2-nucleotide 3'-end-binding pocket made up of the PAZ domain show little effect.

PubMed: 18754009
DOI: 10.1038/nature07315

実験手法

X-RAY DIFFRACTION (2.7 Å)