| SMART accession number: | SM00950
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| Description: |
This domain is found in the protein Piwi and its relatives. The function of this domain is the dsRNA guided hydrolysis of ssRNA. Determination of the crystal structure of Argonaute reveals that PIWI is an RNase H domain, and identifies Argonaute as Slicer, the enzyme that cleaves mRNA in the RNAi RISC complex (PUBMED:15284453) . In addition, Mg+2 dependence and production of 3'-OH and 5' phosphate products are shared characteristics of RNaseH and RISC. The PIWI domain core has a tertiary structure belonging to the RNase H family of enzymes. RNase H fold proteins all have a five-stranded mixed beta-sheet surrounded by helices. By analogy to RNase H enzymes which cleave single-stranded RNA guided by the DNA strand in an RNA/DNA hybrid, the PIWI domain can be inferred to cleave single-stranded RNA, for example mRNA, guided by double stranded siRNA. |
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| Interpro abstract (IPR003165): |
This domain is found in the stem cell self-renewal protein Piwi and its relatives in Drosophila melanogaster [(PUBMED:9851978)]. It has been found in the C-terminal of a number of proteins which also contain the PAZ domain (IPR003100) in their central region, for example the Argonaute proteins. Several of these proteins have been implicated in the development and maintenance of stem cells through the RNA-mediated gene-quelling mechanisms associated with the protein DICER.
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| GO function: | protein binding (GO:0005515) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Cellular role (predicted cellular role)
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Cellular role: transcription
- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Song JJ, Smith SK, Hannon GJ, Joshua-Tor L
- Crystal structure of Argonaute and its implications for RISC sliceractivity.
- Science. 2004; 305: 1434-7
- Display abstract
Argonaute proteins and small interfering RNAs (siRNAs) are the knownsignature components of the RNA interference effector complex RNA-inducedsilencing complex (RISC). However, the identity of "Slicer," the enzymethat cleaves the messenger RNA (mRNA) as directed by the siRNA, has notbeen resolved. Here, we report the crystal structure of the Argonauteprotein from Pyrococcus furiosus at 2.25 angstrom resolution. Thestructure reveals a crescent-shaped base made up of the amino-terminal,middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is heldabove the base by a "stalk"-like region. The PIWI domain (named for theprotein piwi) is similar to ribonuclease H, with a conserved active siteaspartate-aspartate-glutamate motif, strongly implicating Argonaute as"Slicer." The architecture of the molecule and the placement of the PAZand PIWI domains define a groove for substrate binding and suggest amechanism for siRNA-guided mRNA cleavage.
- Cerutti L, Mian N, Bateman A
- Domains in gene silencing and cell differentiation proteins: the novel PAZdomain and redefinition of the Piwi domain.
- Trends Biochem Sci. 2000; 25: 481-2
- Structure (3D structures containing this domain)
3D Structures of Piwi domains in PDB
| PDB code | Main view | Title | | 1u04 |  | Crystal structure of full length argonaute from pyrococcus furiosus |
| 1w9h |  | The structure of a piwi protein from archaeoglobus fulgidus. |
| 1ytu |  | Structural basis for 5'-end-specific recognition of the guide rna strand by the a. fulgidus piwi protein |
| 1yvu |  | Crystal structure of a. aeolicus argonaute |
| 1z25 |  | Structure of p.furiosus argonaute with bound mn2+ |
| 1z26 |  | Structure of pyrococcus furiosus argonaute with bound tungstate |
| 2bgg |  | The structure of a piwi protein from archaeoglobus fulgidus complexed with a 16nt sirna duplex. |
| 2f8s |  | Crystal structure of aa-ago with externally-bound sirna |
| 2f8t |  | Crystal structure of aa-ago with externally-bound sirna |
| 2nub |  | Structure of aquifex aeolicus argonuate |
| 2w42 |  | The structure of a piwi protein from archaeoglobus fulgidus complexed with a 16nt dna duplex. |
| 3dlb |  | Crystal structure of the guide-strand-containing argonaute protein silencing complex |
| 3dlh |  | Crystal structure of the guide-strand-containing argonaute protein silencing complex |
| 3f73 |  | Alignment of guide-target seed duplex within an argonaute silencing complex |
| 3hjf |  | Crystal structure of t. thermophilus argonaute e546 mutant protein complexed with dna guide strand and 15-nt rna target strand |
| 3hk2 |  | Crystal structure of t. thermophilus argonaute n478 mutant protein complexed with dna guide strand and 19-nt rna target strand |
| 3hm9 |  | Crystal structure of t. thermophilus argonaute complexed with dna guide strand and 19-nt rna target strand |
| 3ho1 |  | Crystal structure of t. thermophilus argonaute n546 mutant protein complexed with dna guide strand and 12-nt rna target strand |
| 3hvr |  | Crystal structure of t. thermophilus argonaute complexed with dna guide strand and 19-nt rna target strand with two mg2+ at the cleavage site |
| 3hxm |  | Structure of an argonaute complexed with guide dna and target rna duplex containing two mismatches. |
- Links (links to other resources describing this domain)
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