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[[Image:Unremediated1rpuWithPolyview3D.png|left|300px]]<br />
==Plant Viral Protein p19 Suppression of RNA Silencing==
 
<StructureSection load='' size='350' side='right' caption='p19 dimer and siRNA [[1rpu]]' scene='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/View1/2'>
 
'''3D structure of p19 complexed to siRNA'''
 
 
 
 
==Background==
==Background==
[http://en.wikipedia.org/wiki/RNA_Silencing RNA silencing] is a gene inactivation system in many eukaryotes that relies on tiny RNAs as the targeting molecules. One function of RNA silencing, which is also called [http://en.wikipedia.org/wiki/Post-transcriptional_gene_silencing post-transcriptional gene silencing (PTGS)] or [[RNA Interference|RNA interference]] (RNAi), is to act in surveillance against molecular parasites, such as viruses. Double-stranded RNA triggers the RNA silencing pathway and most plant viruses use a double-stranded RNA to replicate their genome. Various plant viruses have developed evasion techniques to circumvent this surveillance system. In one such evasion strategy, the plant viral protein p19 suppresses a plant's anti-viral RNA silencing response. p19 binds with high affinity to the double-stranded RNA silencing mediator, called [http://en.wikipedia.org/wiki/Small_interfering_RNA siRNA], and this binding sequesters the siRNA, preventing its participation in later steps of RNA silencing.   
[http://en.wikipedia.org/wiki/RNA_Silencing RNA silencing] is a gene inactivation system in many eukaryotes that relies on tiny RNAs as the targeting molecules. One function of RNA silencing, which is also called [http://en.wikipedia.org/wiki/Post-transcriptional_gene_silencing post-transcriptional gene silencing (PTGS)] or [[RNA Interference|RNA interference]] (RNAi), is to act in surveillance against molecular parasites, such as viruses. Double-stranded RNA triggers the RNA silencing pathway and most plant viruses use a double-stranded RNA to replicate their genome. Various plant viruses have developed evasion techniques to circumvent this surveillance system. In one such evasion strategy, the plant viral protein p19 suppresses a plant's anti-viral RNA silencing response. p19 binds with high affinity to the double-stranded RNA silencing mediator, called [http://en.wikipedia.org/wiki/Small_interfering_RNA siRNA], and this binding sequesters the siRNA, preventing its participation in later steps of RNA silencing.   
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siRNAs are generally characterized by their short length (21–26 nt), 2 nt, 3′ overhanging ends, and 5′ phosphate groups. The most efficient silencing is obtained with siRNA duplexes composed of 21-nt sense and 21-nt antisense strands, paired in a manner to have a 2-nt 3' overhang (see [http://www.rockefeller.edu/labheads/tuschl/sirna.html the Tuschl lab's guide] for designing siRNAs)<ref>Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate., Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T, EMBO J. 2001 Dec 3;20(23):6877-88. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11726523 11726523]</ref>.
siRNAs are generally characterized by their short length (21–26 nt), 2 nt, 3′ overhanging ends, and 5′ phosphate groups. The most efficient silencing is obtained with siRNA duplexes composed of 21-nt sense and 21-nt antisense strands, paired in a manner to have a 2-nt 3' overhang (see [http://www.rockefeller.edu/labheads/tuschl/sirna.html the Tuschl lab's guide] for designing siRNAs)<ref>Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate., Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T, EMBO J. 2001 Dec 3;20(23):6877-88. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11726523 11726523]</ref>.
<br>
<br>
Structural studies <ref>Size selective recognition of siRNA by an RNA silencing suppressor., Vargason JM, Szittya G, Burgyan J, Tanaka Hall TM, Cell 2003 Dec 26;115(7):799-811. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14697199 14697199]</ref><ref>Recognition of small interfering RNA by a viral suppressor of RNA silencing., Ye K, Malinina L, Patel D J, Nature 2003 426(6968):874-878. Epub 2003 Dec 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14661029 14661029]</ref> have revealed how p19 from carnation and tomato viruses selectively recognizes the double-stranded siRNA. p19 from the carnation virus is presented on this page; however the results are relevant to both p19 examples as the solved structures are very similar, consistent with the high percent of identity (89%) for the homologous proteins<ref name='alignment'>[[Alignment of 1rpu vs 1r9f|Alignment of Carnation italian ringspot virus p19 (in 1rpu) vs. Tomato bushy stunt virus p19 (in 1r9f)]].</ref>.
Structural studies <ref>Size selective recognition of siRNA by an RNA silencing suppressor., Vargason JM, Szittya G, Burgyan J, Tanaka Hall TM, Cell 2003 Dec 26;115(7):799-811. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14697199 14697199]</ref><ref>Recognition of small interfering RNA by a viral suppressor of RNA silencing., Ye K, Malinina L, Patel D J, Nature 2003 426(6968):874-878. Epub 2003 Dec 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14661029 14661029]</ref> have revealed how p19 from carnation and tomato viruses selectively recognizes the double-stranded siRNA. p19 from the carnation virus is presented on this page; however the results are relevant to both p19 examples as the solved structures are very similar, consistent with the high percent of identity (89%) for the homologous proteins<ref name='alignment'>[[Alignment of 1rpu vs 1r9f|Alignment of Carnation italian ringspot virus p19 (in 1rpu) vs. Tomato bushy stunt virus p19 (in 1r9f)]].</ref>. See [[Alignment of 1rpu vs 1r9f]].
 
==Results==
==Results==
{{Structure
|PDB= 1rpu |SIZE=400|SCENE=User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/View1/2|CAPTION= p19 and siRNA [[1rpu]], resolution 2.50&Aring; (<scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/View1/2'>initial scene</scene>)
|SITE=
|LIGAND=
|ACTIVITY=
|GENE=
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'><!--[http://www-unix.oit.umass.edu/~wdecatur/p19tutorial/ Explorable Tour], Eric Martz felt no one would look here-->[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rpu OCA], [http://www.ebi.ac.uk/pdbsum/1rpu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rpu RCSB]</span>
}}
The X-ray crystal structure of <scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/Rnaprotein1rpu/3'>p19 complexed with double-stranded siRNA</scene> includes both {{User:Wayne Decatur/Template ColorKey Composition lcprotein}} and {{Template:ColorKey Composition RNA}} in the complex. {{Link Toggle FancyCartoonHighQualityView}}.
The X-ray crystal structure of <scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/Rnaprotein1rpu/3'>p19 complexed with double-stranded siRNA</scene> includes both {{User:Wayne Decatur/Template ColorKey Composition lcprotein}} and {{Template:ColorKey Composition RNA}} in the complex. {{Link Toggle FancyCartoonHighQualityView}}.


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<scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/8strandcontinuousbetasheet/3'>The p19 dimer</scene> forms a <font color = '#cdcd00'>continuous eight-stranded beta-sheet</font>.
<scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/8strandcontinuousbetasheet/3'>The p19 dimer</scene> forms a <font color = '#cdcd00'>continuous eight-stranded beta-sheet</font>.


The <font color = '#cdcd00'>continuous eight-stranded beta-sheet</font> of <scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/Sheetcradlesminorgroove/4'>the p19 dimer cradles the minor groove of the duplex region</scene> of the double stranded siRNA. This is unusual because most proteins use loops and helices to bind double-stranded RNA, for example, see [[1di2]], [[2zi0]], [[2hvy]] or [[2az0]].
The <font color = '#cdcd00'>continuous eight-stranded beta-sheet</font> of <scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/Sheetcradlesminorgroove/4'>the p19 dimer cradles the minor groove of the duplex region</scene> of the double stranded siRNA. This is unusual because most proteins use loops and helices to bind double-stranded RNA, for example, see [[1di2]], [[2zi0]], [[2hvy]] or [[2az0]].  For more detais see [[P19 complexed with 19-bp small interfering RNA]].




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==3D structures of protein p19==
==3D structures of protein p19==


[[1rpu]] – P19 + SiRNA – Carnation italian ringspot virus<br />
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
[[1rpf]] - P19 (mutant) + SiRNA –Tomato bushy stunt virus<br />
 
[[3lzl]],[[3lzn]],[[3lzo]],[[3lzp]],[[3lzq]],[[3lzr]] – P19 – ''Campylobacter jejuni''
[[1rpu]], [[6bjv]] – CirvP19 + SiRNA – Carnation italian ringspot virus<br />
[[6bjh]], [[6bjg]] - CirvP19 (mutant) + SiRNA<br />
[[4j39]], [[4j5v]],  [[4jgn]], [[4jnx]], [[4knq]], [[4ktg]] - TbsvP19 + SiRNA - Tomato bushy stunt virus <br />
[[1rpf]], [[4jk0]], [[4kq0]] - TbsvP19 (mutant) + SiRNA<br />
[[3lzl]],[[3lzn]],[[3lzo]],[[3lzp]],[[3lzq]],[[3lzr]], [[5i0w]], [[5i0v]]  – P19 – ''Campylobacter jejuni''<br />
[[5dof]] - TtP19 – ''Tetrahymena thermophila''<br />
[[5doi]] - TtP19 + P45 <br />
[[6cus]] - RsvP19 M-domain (mutant) + inositol-hexakisphosphate – Rous sarcoma virus - NMR<br />
[[6cv8]], [[6cw4]] - RsvP19 M-domain (mutant) + inositol-trisphosphate – Rous sarcoma virus - NMR<br />
[[8h2i]] - RbcvP19 in capsid – Paramecium bursara chlorella virus <br />


==Related Structures and Topics==
==Related Structures and Topics==
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==Additional Literature and Resources==
==Additional Literature and Resources==
*[http://www-unix.oit.umass.edu/~wdecatur/p19tutorial/ Tour of p19 bound to an siRNA] by Wayne Decatur, in an exploration-friendly interface that is adapted from Eric Martz's [http://molvis.sdsc.edu/fgij/index.htm FirstGlance in Jmol]<br>
*Structural basis for RNA-silencing suppression by Tomato aspermy virus protein 2b., Chen HY, Yang J, Lin C, Yuan YA, EMBO Rep. 2008 Aug;9(8):754-60. Epub 2008 Jul 4.PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18600235 18600235]<br>
*Structural basis for RNA-silencing suppression by Tomato aspermy virus protein 2b., Chen HY, Yang J, Lin C, Yuan YA, EMBO Rep. 2008 Aug;9(8):754-60. Epub 2008 Jul 4.PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18600235 18600235]<br>
*The structure of the flock house virus B2 protein, a viral suppressor of RNA interference, shows a novel mode of double-stranded RNA recognition., Lingel A, Simon B, Izaurralde E, Sattler M. EMBO Rep. 2005 Dec;6(12):1149-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16270100 16270100]<br>
*The structure of the flock house virus B2 protein, a viral suppressor of RNA interference, shows a novel mode of double-stranded RNA recognition., Lingel A, Simon B, Izaurralde E, Sattler M. EMBO Rep. 2005 Dec;6(12):1149-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16270100 16270100]<br>
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<ref group="xtra">PMID:16419274</ref>
<ref group="xtra">PMID:16419274</ref>
<references group="xtra"/>  
<references group="xtra"/>  
</StructureSection>
[[Category: RNA Silencing]]
[[Category: RNA Silencing]]
[[Category: post-transcriptional gene silencing (PTGS)]]
[[Category: post-transcriptional gene silencing (PTGS)]]