|
|
| (14 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2dok.gif|left|200px]]<br /> | |
| - | <applet load="2dok" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2dok, resolution 1.80Å" /> | |
| - | '''Crystal structure of the PIN domain of human EST1A'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of the PIN domain of human EST1A== |
| - | Saccharomyces cerevisiae Est1p is a telomerase-associated protein, essential for telomere length homeostasis. hEST1A is one of the three, human Est1p homologues and is considered to be involved not only in, regulation of telomere elongation or capping but also in nonsense-mediated, degradation of RNA. hEST1A is composed of two conserved regions, Est1p, homology and PIN (PilT N-terminus) domains. The present study shows the, crystal structure of the PIN domain at 1.8 A resolution. The overall, structure is composed of an alpha/beta fold or a core structure similar to, the counterpart of 5' nucleases and an extended structure absent from, archaeal PIN-domain proteins and 5' nucleases. The structural properties, of the PIN domain indicate its putative active center consisting of, invariant acidic amino acid residues, which is geometrically similar to, the active center of 5' nucleases and an archaeal PAE2754 PIN-domain, protein associated with exonuclease activity.
| + | <StructureSection load='2dok' size='340' side='right'caption='[[2dok]], [[Resolution|resolution]] 1.80Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==About this Structure== | + | <table><tr><td colspan='2'>[[2dok]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DOK FirstGlance]. <br> |
| - | 2DOK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2DOK OCA].
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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=2dok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dok OCA], [https://pdbe.org/2dok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dok RCSB], [https://www.ebi.ac.uk/pdbsum/2dok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dok ProSAT]</span></td></tr> |
| - | ==Reference== | + | </table> |
| - | Crystal structure of the PIN domain of human telomerase-associated protein EST1A., Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M, Proteins. 2007 Sep 1;68(4):980-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17557331 17557331]
| + | == Function == |
| | + | [https://www.uniprot.org/uniprot/EST1A_HUMAN EST1A_HUMAN] Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).<ref>PMID:12676087</ref> <ref>PMID:12699629</ref> <ref>PMID:18974281</ref> <ref>PMID:19060897</ref> <ref>PMID:17053788</ref> Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.<ref>PMID:12676087</ref> <ref>PMID:12699629</ref> <ref>PMID:18974281</ref> <ref>PMID:19060897</ref> <ref>PMID:17053788</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/2dok_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2dok ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Takeshita, D.]] | + | [[Category: Takeshita D]] |
| - | [[Category: telomerase-associated protein]]
| + | |
| - | [[Category: unknown function]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:38:53 2007''
| + | |
| Structural highlights
Function
EST1A_HUMAN Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).[1] [2] [3] [4] [5] Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.[6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol. 2003 Apr 1;13(7):568-74. PMID:12676087
- ↑ Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L. Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. PMID:12699629
- ↑ Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. doi: 10.1261/rna.1386208. Epub 2008 Oct 30. PMID:18974281 doi:http://dx.doi.org/10.1261/rna.1386208
- ↑ Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. doi: 10.1038/nsmb.1530. Epub 2008 Dec , 7. PMID:19060897 doi:http://dx.doi.org/10.1038/nsmb.1530
- ↑ Glavan F, Behm-Ansmant I, Izaurralde E, Conti E. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788
- ↑ Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol. 2003 Apr 1;13(7):568-74. PMID:12676087
- ↑ Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L. Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. PMID:12699629
- ↑ Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. doi: 10.1261/rna.1386208. Epub 2008 Oct 30. PMID:18974281 doi:http://dx.doi.org/10.1261/rna.1386208
- ↑ Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. doi: 10.1038/nsmb.1530. Epub 2008 Dec , 7. PMID:19060897 doi:http://dx.doi.org/10.1038/nsmb.1530
- ↑ Glavan F, Behm-Ansmant I, Izaurralde E, Conti E. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788
|
