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| | ==Crystal Structure of human Hiwi1 PAZ domain (residues 277-399) in complex with 14-mer RNA (12-bp + 2-nt overhang) containing 2'-OCH3 at its 3'-end== | | ==Crystal Structure of human Hiwi1 PAZ domain (residues 277-399) in complex with 14-mer RNA (12-bp + 2-nt overhang) containing 2'-OCH3 at its 3'-end== |
| - | <StructureSection load='3o6e' size='340' side='right' caption='[[3o6e]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3o6e' size='340' side='right'caption='[[3o6e]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o6e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O6E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o6e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O6E FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o3i|3o3i]], [[3o7v|3o7v]], [[3o7x|3o7x]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3o3i|3o3i]], [[3o7v|3o7v]], [[3o7x|3o7x]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HIWI, Piwi-like protein 1, PIWIL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HIWI, Piwi-like protein 1, PIWIL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o6e OCA], [http://pdbe.org/3o6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o6e RCSB], [http://www.ebi.ac.uk/pdbsum/3o6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o6e ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3o6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o6e OCA], [https://pdbe.org/3o6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o6e RCSB], [https://www.ebi.ac.uk/pdbsum/3o6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o6e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PIWL1_HUMAN PIWL1_HUMAN]] Plays a central role during spermatogenesis by repressing transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (By similarity). Isoform 3 may be a negative developmental regulator.<ref>PMID:12037681</ref> <ref>PMID:14749716</ref> <ref>PMID:16287078</ref> | + | [[https://www.uniprot.org/uniprot/PIWL1_HUMAN PIWL1_HUMAN]] Plays a central role during spermatogenesis by repressing transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (By similarity). Isoform 3 may be a negative developmental regulator.<ref>PMID:12037681</ref> <ref>PMID:14749716</ref> <ref>PMID:16287078</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ma, J B]] | | [[Category: Ma, J B]] |
| | [[Category: Patel, D J]] | | [[Category: Patel, D J]] |
| Structural highlights
Function
[PIWL1_HUMAN] Plays a central role during spermatogenesis by repressing transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (By similarity). Isoform 3 may be a negative developmental regulator.[1] [2] [3]
Publication Abstract from PubMed
Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2(')-OCH(3)) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role in genome defense against transposable elements, thereby protecting the genome against transposon-induced defects in gametogenesis and fertility. Humans contain four Piwi family proteins designated Hiwi1, Hiwi2, Hiwi3, and Hili. We report on the structures of Hili-PAZ (Piwi/Argonaute/Zwille) domain in the free state and Hiwi1 PAZ domain bound to self-complementary 14-mer RNAs (12-bp + 2-nt overhang) containing 2(')-OCH(3) and 2'-OH at their 3' ends. These structures explain the molecular basis underlying accommodation of the 2(')-OCH(3) group within a preformed Hiwi1 PAZ domain binding pocket, whose hydrophobic characteristics account for the preferential binding of 2(')-OCH(3) over 2'-OH 3' ends. These results contrast with the more restricted binding pocket for the human Ago1 PAZ domain, which exhibits a reverse order, with preferential binding of 2'-OH over 2(')-OCH(3) 3' ends.
Inaugural Article: Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains.,Tian Y, Simanshu DK, Ma JB, Patel DJ Proc Natl Acad Sci U S A. 2010 Dec 30. PMID:21193640[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002 Jun 6;21(25):3988-99. PMID:12037681 doi:10.1038/sj.onc.1205505
- ↑ Tahbaz N, Kolb FA, Zhang H, Jaronczyk K, Filipowicz W, Hobman TC. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. EMBO Rep. 2004 Feb;5(2):189-94. Epub 2004 Jan 16. PMID:14749716 doi:10.1038/sj.embor.7400070
- ↑ Liu X, Sun Y, Guo J, Ma H, Li J, Dong B, Jin G, Zhang J, Wu J, Meng L, Shou C. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer. 2006 Apr 15;118(8):1922-9. PMID:16287078 doi:10.1002/ijc.21575
- ↑ Tian Y, Simanshu DK, Ma JB, Patel DJ. Inaugural Article: Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proc Natl Acad Sci U S A. 2010 Dec 30. PMID:21193640 doi:10.1073/pnas.1017762108
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