P19: Difference between revisions

[[Image:Unremediated1rpuWithPolyview3D.png|left|300px]]<br />

 

 

'''3D structure of p19 complexed to siRNA'''

 

 

 

 

[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 [http://en.wikipedia.org/wiki/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 plants 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.   

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 selectively recognizes the double-stranded siRNA.

 

 

 

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.

<small><b><font face = 'courier'>

<!-- By setting font to courier, I can use non-proportional font. Whereas by default, rest of Protopedia is proportional -->

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<font color = '#00FF00'>5'-pCGUACGCGUCACGCGUACGUU-OH-3'</font><br>&nbsp;&nbsp;

&nbsp;&nbsp;&nbsp;&nbsp;<font color = '#6060ff'>3'-OH-UUGCAUGCGCACUGCGCAUGCp-5'</font></font></b>

</small><br>

<scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/P19isadimer/4'>a dimer</scene>.<br>

Each <scene name='User:Wayne_Decatur/Plant_Viral_Protein_p19_Suppression_of_RNA_Silencing/Secondarystructureofmonomer/4'>monomer of p19</scene> is made of <font color = '#ff0080'>five alpha-helices</font> and a <font color='#cdcd00'>four-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]].

Most unprecedented is the method of size selection where p19 acts as a molecular caliper reading the size of the substrate. The <font color = 'orange'>aromatic rings of two tryptophan residues (W39 and W42)</font> project from the 'reading' helix near the N-terminus of each of the two p19 monomers, stacking on the terminal base-pairs and symmetrically bracketing the ends of the duplex region of the siRNA. Thus the p19 'caliper' measures and specifically selects siRNA based on the size of the duplex region. The ability of p19 to efficiently accommodate binding of duplexes ranging from 19 to 21 bp could originate in structural plasticity of the distance separating the two 'reading head' helices. Each  'reading' helix is connected to the structured core of p19 by a short flexible loop and several side-chain interactions this presumably allows some flexibility in the positioning of the RNA end-capping tryptophan residues. Many other structures use aromatic rings to stack on nucleotide bases and cap strands in helices, see [[1gm5|F204 and Y208 of 1gm5]], [[1msw|W639 of 1msw]] and [[1qln]].<br>  

*[[User:Wayne Decatur/Suppression of RNA Silencing by Viruses|Suppression of RNA Silencing by Viruses]]

*[[User:Wayne Decatur/Tomato aspermy virus protein 2b Suppression of RNA Silencing|Tomato aspermy virus protein 2b Suppression of RNA Silencing]]

*[[User:Wayne Decatur/Flock house virus B2 protein Suppression of RNA Silencing|Flock house virus B2 protein Suppression of RNA Silencing]]

[[CAtegory: Protein complex]]