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Structure of the guide-strand-containing argonaute silencing complex

Author

Listed:
  • Yanli Wang

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA)

  • Gang Sheng

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA)

  • Stefan Juranek

    (Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York 10065, USA)

  • Thomas Tuschl

    (Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York 10065, USA)

  • Dinshaw J. Patel

    (Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA)

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.

Suggested Citation

  • Yanli Wang & Gang Sheng & Stefan Juranek & Thomas Tuschl & Dinshaw J. Patel, 2008. "Structure of the guide-strand-containing argonaute silencing complex," Nature, Nature, vol. 456(7219), pages 209-213, November.
  • Handle: RePEc:nat:nature:v:456:y:2008:i:7219:d:10.1038_nature07315
    DOI: 10.1038/nature07315
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    Cited by:

    1. Sarah Willkomm & Leonhard Jakob & Kevin Kramm & Veronika Graus & Julia Neumeier & Gunter Meister & Dina Grohmann, 2022. "Single-molecule FRET uncovers hidden conformations and dynamics of human Argonaute 2," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Yonghua Wang & Yan Li & Zhi Ma & Wei Yang & Chunzhi Ai, 2010. "Mechanism of MicroRNA-Target Interaction: Molecular Dynamics Simulations and Thermodynamics Analysis," PLOS Computational Biology, Public Library of Science, vol. 6(7), pages 1-19, July.
    3. Bin Yang & Haonan Wang & Jilie Kong & Xueen Fang, 2024. "Long-term monitoring of ultratrace nucleic acids using tetrahedral nanostructure-based NgAgo on wearable microneedles," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Lidiya Lisitskaya & Yeonoh Shin & Aleksei Agapov & Anna Olina & Ekaterina Kropocheva & Sergei Ryazansky & Alexei A. Aravin & Daria Esyunina & Katsuhiko S. Murakami & Andrey Kulbachinskiy, 2022. "Programmable RNA targeting by bacterial Argonaute nucleases with unconventional guide binding and cleavage specificity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Carolien Bastiaanssen & Pilar Bobadilla Ugarte & Kijun Kim & Giada Finocchio & Yanlei Feng & Todd A. Anzelon & Stephan Köstlbacher & Daniel Tamarit & Thijs J. G. Ettema & Martin Jinek & Ian J. MacRae , 2024. "RNA-guided RNA silencing by an Asgard archaeal Argonaute," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Xiangkai Zhen & Xiaolong Xu & Le Ye & Song Xie & Zhijie Huang & Sheng Yang & Yanhui Wang & Jinyu Li & Feng Long & Songying Ouyang, 2024. "Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Hanlun Jiang & Fu Kit Sheong & Lizhe Zhu & Xin Gao & Julie Bernauer & Xuhui Huang, 2015. "Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement," PLOS Computational Biology, Public Library of Science, vol. 11(7), pages 1-21, July.
    8. Bidur Paudel & Si-Yeon Jeong & Carolina Pena Martinez & Alexis Rickman & Ashley Haluck-Kangas & Elizabeth T. Bartom & Kristina Fredriksen & Amira Affaneh & John A. Kessler & Joseph R. Mazzulli & Andre, 2024. "Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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