2hwx: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2hwx.gif|left|200px]]<br /><applet load="2hwx" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2hwx, resolution 1.90&Aring;" />
-'''Structure of human SMG6 E1282C PIN domain mutant.'''<br />
-==Overview==
+==Structure of human SMG6 E1282C PIN domain mutant.==
-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.
+<StructureSection load='2hwx' size='340' side='right'caption='[[2hwx]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2hwx]] is a 1 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=2HWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HWX FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</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=2hwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwx OCA], [https://pdbe.org/2hwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hwx RCSB], [https://www.ebi.ac.uk/pdbsum/2hwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hwx ProSAT]</span></td></tr>
+</table>
+== 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/hw/2hwx_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=2hwx ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-HWX 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2HWX OCA].
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
+== References ==
-==Reference==
+<references/>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17053788 17053788]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[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]]
-[[Category: nmd]]
-[[Category: p bodies]]
-[[Category: rna degradation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:46:40 2008''