3sag

From Proteopedia

(Difference between revisions)

Revision as of 14:36, 24 December 2014

Crystal structure of the human RRP6 catalytic domain with D313N mutation in the active site

Structural highlights

3sag is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3saf, 3sah
Gene:	EXOSC10, PMSCL, PMSCL2, RRP6 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[EXOSX_HUMAN] Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. EXOSC10 has 3'-5' exonuclease activity (By similarity). EXOSC10 is required for nucleolar localization of C1D and probably mediates the association of SKIV2L2, C1D and MPP6 wth the RNA exosome involved in the maturation of 5.8S rRNA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

The eukaryotic RNA exosome is a highly conserved multi-subunit complex that catalyzes degradation and processing of coding and noncoding RNA. A noncatalytic nine-subunit exosome core interacts with Rrp44 and Rrp6, two subunits that possess processive and distributive 3'-5' exoribonuclease activity, respectively. While both Rrp6 and Rrp44 are responsible for RNA processing in budding yeast, Rrp6 may play a more prominent role in processing, as it has been demonstrated to be inhibited by stable RNA secondary structure in vitro and because the null allele in budding yeast leads to the buildup of specific structured RNA substrates. Human RRP6, otherwise known as PM/SCL-100 or EXOSC10, shares sequence similarity to budding yeast Rrp6 and is proposed to catalyze 3'-5' exoribonuclease activity on a variety of nuclear transcripts including ribosomal RNA subunits, RNA that has been poly-adenylated by TRAMP, as well as other nuclear RNA transcripts destined for processing and/or destruction. To characterize human RRP6, we expressed the full-length enzyme as well as truncation mutants that retain catalytic activity, compared their activities to analogous constructs for Saccharomyces cerevisiae Rrp6, and determined the X-ray structure of a human construct containing the exoribonuclease and HRDC domains that retains catalytic activity. Structural data show that the human active site is more exposed when compared to the yeast structure, and biochemical data suggest that this feature may play a role in the ability of human RRP6 to productively engage and degrade structured RNA substrates more effectively than the analogous budding yeast enzyme.

Activities of human RRP6 and structure of the human RRP6 catalytic domain.,Januszyk K, Liu Q, Lima CD RNA. 2011 Jun 24. PMID:21705430^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lejeune F, Li X, Maquat LE. Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol Cell. 2003 Sep;12(3):675-87. PMID:14527413
↑ West S, Gromak N, Norbury CJ, Proudfoot NJ. Adenylation and exosome-mediated degradation of cotranscriptionally cleaved pre-messenger RNA in human cells. Mol Cell. 2006 Feb 3;21(3):437-43. PMID:16455498 doi:http://dx.doi.org/10.1016/j.molcel.2005.12.008
↑ Schilders G, van Dijk E, Pruijn GJ. C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic Acids Res. 2007;35(8):2564-72. Epub 2007 Apr 4. PMID:17412707 doi:http://dx.doi.org/10.1093/nar/gkm082
↑ van Dijk EL, Schilders G, Pruijn GJ. Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA. 2007 Jul;13(7):1027-35. Epub 2007 Jun 1. PMID:17545563 doi:10.1261/rna.575107
↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
↑ Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, Schierup MH, Jensen TH. RNA exosome depletion reveals transcription upstream of active human promoters. Science. 2008 Dec 19;322(5909):1851-4. doi: 10.1126/science.1164096. Epub 2008, Dec 4. PMID:19056938 doi:10.1126/science.1164096
↑ de Almeida SF, Garcia-Sacristan A, Custodio N, Carmo-Fonseca M. A link between nuclear RNA surveillance, the human exosome and RNA polymerase II transcriptional termination. Nucleic Acids Res. 2010 Dec;38(22):8015-26. doi: 10.1093/nar/gkq703. Epub 2010, Aug 10. PMID:20699273 doi:http://dx.doi.org/10.1093/nar/gkq703
↑ Slomovic S, Fremder E, Staals RH, Pruijn GJ, Schuster G. Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7407-12. doi:, 10.1073/pnas.0910621107. Epub 2010 Apr 5. PMID:20368444 doi:10.1073/pnas.0910621107
↑ Januszyk K, Liu Q, Lima CD. Activities of human RRP6 and structure of the human RRP6 catalytic domain. RNA. 2011 Jun 24. PMID:21705430 doi:10.1261/rna.2763111

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sag"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3sag]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SAG FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3saf|3saf]], [[3sah|3sah]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3saf|3saf]], [[3sah|3sah]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EXOSC10, PMSCL, PMSCL2, RRP6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EXOSC10, PMSCL, PMSCL2, RRP6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sag OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sag RCSB], [http://www.ebi.ac.uk/pdbsum/3sag PDBsum]</span></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=3sag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sag OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sag RCSB], [http://www.ebi.ac.uk/pdbsum/3sag PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/EXOSX_HUMAN EXOSX_HUMAN]] Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. EXOSC10 has 3'-5' exonuclease activity (By similarity). EXOSC10 is required for nucleolar localization of C1D and probably mediates the association of SKIV2L2, C1D and MPP6 wth the RNA exosome involved in the maturation of 5.8S rRNA.<ref>PMID:14527413</ref> <ref>PMID:16455498</ref> <ref>PMID:17412707</ref> <ref>PMID:17545563</ref> <ref>PMID:18172165</ref> <ref>PMID:19056938</ref> <ref>PMID:20699273</ref> <ref>PMID:20368444</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 16: @@
 Activities of human RRP6 and structure of the human RRP6 catalytic domain.,Januszyk K, Liu Q, Lima CD RNA. 2011 Jun 24. PMID:21705430<ref>PMID:21705430</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 == References ==
@@ Line 21: / Line 23: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Januszyk, K.]]
+[[Category: Januszyk, K]]
-[[Category: Lima, C D.]]
+[[Category: Lima, C D]]
-[[Category: Liu, Q.]]
+[[Category: Liu, Q]]
 [[Category: Exoribonuclease]]
 [[Category: Hydrolase]]
 [[Category: Rna exosome]]

3sag

From Proteopedia

Revision as of 14:36, 24 December 2014

Crystal structure of the human RRP6 catalytic domain with D313N mutation in the active site

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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