2hwx

From Proteopedia

(Difference between revisions)

Revision as of 23:13, 24 December 2014

Structure of human SMG6 E1282C PIN domain mutant.

Structural highlights

2hwx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2hww
Gene:	EST1A (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

Publication Abstract from PubMed

SMG6 and SMG5 are essential factors in nonsense-mediated mRNA decay, a conserved pathway that degrades mRNAs with premature translation termination codons. Both SMG5 and SMG6 have been predicted to contain a C-terminal PIN (PilT N-terminus) domain, present in proteins with ribonuclease activity. We have determined the structures of human SMG5 and SMG6 PIN domains. Although they share a similar overall fold related to ribonucleases of the RNase H family, they have local differences at the putative active site. SMG6 has the canonical triad of acidic residues that are crucial in RNase H for nuclease activity, while SMG5 lacks key catalytic residues. The structural differences are reflected at the functional level. Only the PIN domain of SMG6 has degradation activity on single-stranded RNA in vitro. This difference in catalytic activity is conserved in Drosophila, where an SMG6 with an inactive PIN domain inhibits NMD in a dominant-negative manner. Our findings suggest that the NMD machinery has intrinsic nuclease activity that is likely to contribute to the rapid decay of mRNAs that terminate translation prematurely.

Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex.,Glavan F, Behm-Ansmant I, Izaurralde E, Conti E EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788^[11]

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

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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hwx"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2hwx]] is a 1 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=2HWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HWX FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hww|2hww]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hww|2hww]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EST1A ([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">EST1A ([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=2hwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hwx RCSB], [http://www.ebi.ac.uk/pdbsum/2hwx 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=2hwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hwx RCSB], [http://www.ebi.ac.uk/pdbsum/2hwx PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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]]
@@ Line 30: / Line 32: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Behm-Ansmant, I.]]
+[[Category: Behm-Ansmant, I]]
-[[Category: Conti, E.]]
+[[Category: Conti, E]]
-[[Category: Glavan, F.]]
+[[Category: Glavan, F]]
-[[Category: Izaurralde, E.]]
+[[Category: Izaurralde, E]]
 [[Category: Decay]]
 [[Category: Est1a]]

2hwx

From Proteopedia

Revision as of 23:13, 24 December 2014

Structure of human SMG6 E1282C PIN domain mutant.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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