Crystal structure of argonaute and its implications for RISC slicer activity

Song, J. J., Smith, S. K., Hannon, G. J., Joshua-Tor, L. (September 2004) Crystal structure of argonaute and its implications for RISC slicer activity. Science, 305 (5689). pp. 1434-1437. ISSN 0036-8075 (Public Dataset)

URL: http://www.ncbi.nlm.nih.gov/pubmed/15284453
DOI: 10.1126/science.1102514

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.

Item Type: Paper
Uncontrolled Keywords: PAZ DOMAIN RISC PAZ domain ESCHERICHIA-COLI escherichia coli escherichia-coli RNA INTERFERENCE RNA inteference RNAi DROSOPHILA Drosophila COMPLEX complex ENDONUCLEASE endonuclease INTEGRASE integrase SIRNAS siRNA CORE core TRANSPOSITION transposition
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Joshua-Tor lab
School of Biological Sciences > Publications
Depositing User: CSHL Librarian
Date: September 2004
Date Deposited: 26 Jan 2012 15:55
Last Modified: 05 Sep 2017 18:49
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/22484

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