DOI: 10.1126/science.1102514. Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity

Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity

10.1126/science.1102514

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Argonaute proteins and small interfering RNAs (siRNAs) are the known signature components of the RNA interference effector complex RNA-induced silencing complex (RISC). However, the identity of “Slicer,” the enzyme that cleaves the messenger RNA (mRNA) as directed by the siRNA, has not been resolved. Here, we report the crystal structure of the Argonaute protein from Pyrococcus furiosus at 2.25 angstrom resolution. The structure reveals a crescent-shaped base made up of the amino-terminal, middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held above the base by a “stalk”-like region. The PIWI domain (named for the protein piwi) is similar to ribonuclease H, with a conserved active site aspartate-aspartate-glutamate motif, strongly implicating Argonaute as “Slicer.” The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage.

Bibliography

Song, J.-J., Smith, S. K., Hannon, G. J., & Joshua-Tor, L. (2004). Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity. Science, 305(5689), 1434â1437.

Authors 4

Ji-Joon Song (first)
Stephanie K. Smith (additional)
Gregory J. Hannon (additional)
Leemor Joshua-Tor (additional)

References 31 Referenced 1,147

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Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
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10.1126/science.1102513
We thank E. Enemark for help with data collection R. Martienssen and members of the Joshua-Tor laboratory for helpful discussions and M. Becker (beamline X25) for support with data collection at the National Synchrotron Light Source (NSLS). The NSLS is supported by the U.S. Department of Energy Division of Material Sciences and Division of Chemical Sciences. J.-J.S. is a Bristol-Myers Squibb Predoctoral Fellow. Coordinates have been deposited in the Protein Data Bank (accession code 1U04).

Dates

Type	When
Created	21 years, 1 month ago (July 29, 2004, 8:26 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 10:10 p.m.)
Indexed	38 minutes ago (Sept. 2, 2025, 9:39 p.m.)
Issued	20 years, 11 months ago (Sept. 3, 2004)
Published	20 years, 11 months ago (Sept. 3, 2004)
Published Print	20 years, 11 months ago (Sept. 3, 2004)

Funders 0

None

BibTeX

@article{Song_2004, title={Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity}, volume={305}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1102514}, DOI={10.1126/science.1102514}, number={5689}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Song, Ji-Joon and Smith, Stephanie K. and Hannon, Gregory J. and Joshua-Tor, Leemor}, year={2004}, month=sep, pages={1434–1437} }

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