1ytu
From Proteopedia
(New page: 200px<br /><applet load="1ytu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ytu, resolution 2.50Å" /> '''Structural basis for...) |
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| - | [[Image:1ytu.gif|left|200px]]<br /><applet load="1ytu" size=" | + | [[Image:1ytu.gif|left|200px]]<br /><applet load="1ytu" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ytu, resolution 2.50Å" /> | caption="1ytu, resolution 2.50Å" /> | ||
'''Structural basis for 5'-end-specific recognition of the guide RNA strand by the A. fulgidus PIWI protein'''<br /> | '''Structural basis for 5'-end-specific recognition of the guide RNA strand by the A. fulgidus PIWI protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | RNA interference (RNAi) is a conserved sequence-specific gene regulatory | + | RNA interference (RNAi) is a conserved sequence-specific gene regulatory mechanism mediated by the RNA-induced silencing complex (RISC), which is composed of a single-stranded guide RNA and an Argonaute protein. The PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC. Here we report the crystal structure of Archaeoglobus fulgidus Piwi protein bound to double-stranded RNA, thereby identifying the binding pocket for guide-strand 5'-end recognition and providing insight into guide-strand-mediated messenger RNA target recognition. The phosphorylated 5' end of the guide RNA is anchored within a highly conserved basic pocket, supplemented by the carboxy-terminal carboxylate and a bound divalent cation. The first nucleotide from the 5' end of the guide RNA is unpaired and stacks over a conserved tyrosine residue, whereas successive nucleotides form a four-base-pair RNA duplex. Mutation of the corresponding amino acids that contact the 5' phosphate in human Ago2 resulted in attenuated mRNA cleavage activity. Our structure of the Piwi-RNA complex, and that determined elsewhere, provide direct support for the 5' region of the guide RNA serving as a nucleation site for pairing with target mRNA and for a fixed distance separating the RISC-mediated mRNA cleavage site from the anchored 5' end of the guide RNA. |
==About this Structure== | ==About this Structure== | ||
| - | 1YTU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YTU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YTU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Archaeoglobus fulgidus dsm 4304]] | [[Category: Archaeoglobus fulgidus dsm 4304]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ma, J | + | [[Category: Ma, J B.]] |
[[Category: Meister, G.]] | [[Category: Meister, G.]] | ||
| - | [[Category: Patel, D | + | [[Category: Patel, D J.]] |
[[Category: Pei, Y.]] | [[Category: Pei, Y.]] | ||
[[Category: Tuschl, T.]] | [[Category: Tuschl, T.]] | ||
| - | [[Category: Yuan, Y | + | [[Category: Yuan, Y R.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: protein-rna complex]] | [[Category: protein-rna complex]] | ||
[[Category: rna duplex]] | [[Category: rna duplex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:09:02 2008'' |
Revision as of 14:09, 21 February 2008
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Structural basis for 5'-end-specific recognition of the guide RNA strand by the A. fulgidus PIWI protein
Overview
RNA interference (RNAi) is a conserved sequence-specific gene regulatory mechanism mediated by the RNA-induced silencing complex (RISC), which is composed of a single-stranded guide RNA and an Argonaute protein. The PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC. Here we report the crystal structure of Archaeoglobus fulgidus Piwi protein bound to double-stranded RNA, thereby identifying the binding pocket for guide-strand 5'-end recognition and providing insight into guide-strand-mediated messenger RNA target recognition. The phosphorylated 5' end of the guide RNA is anchored within a highly conserved basic pocket, supplemented by the carboxy-terminal carboxylate and a bound divalent cation. The first nucleotide from the 5' end of the guide RNA is unpaired and stacks over a conserved tyrosine residue, whereas successive nucleotides form a four-base-pair RNA duplex. Mutation of the corresponding amino acids that contact the 5' phosphate in human Ago2 resulted in attenuated mRNA cleavage activity. Our structure of the Piwi-RNA complex, and that determined elsewhere, provide direct support for the 5' region of the guide RNA serving as a nucleation site for pairing with target mRNA and for a fixed distance separating the RISC-mediated mRNA cleavage site from the anchored 5' end of the guide RNA.
About this Structure
1YTU is a Single protein structure of sequence from Archaeoglobus fulgidus dsm 4304 with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein., Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ, Nature. 2005 Mar 31;434(7033):666-70. PMID:15800629
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