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)
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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