1YVU

Crystal structure of A. aeolicus Argonaute

Summary for 1YVU

• Entry DOI: 10.2210/pdb1yvu/pdb
• Descriptor: hypothetical protein aq_1447, CALCIUM ION (3 entities in total)
• Functional Keywords: rnase h fold, rna binding protein, gene regulation
• Biological source: Aquifex aeolicus
• Total number of polymer chains: 1
• Total formula weight: 83585.83

Authors

Yuan, Y.R.,Pei, Y.,Ma, J.B.,Kuryavyi, V.,Zhadina, M.,Meister, G.,Chen, H.Y.,Dauter, Z.,Tuschl, T.,Patel, D.J. (deposition date: 2005-02-16, release date: 2005-08-09, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)