2nnt: Difference between revisions

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[[Image:2nnt.gif|left|200px]]<br /><applet load="2nnt" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2nnt" />
'''General structural motifs of amyloid protofilaments'''<br />


==Overview==
==General structural motifs of amyloid protofilaments==
<StructureSection load='2nnt' size='340' side='right'caption='[[2nnt]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nnt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NNT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NNT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solid-state NMR</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=2nnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnt OCA], [https://pdbe.org/2nnt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nnt RCSB], [https://www.ebi.ac.uk/pdbsum/2nnt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nnt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TCRG1_HUMAN TCRG1_HUMAN] Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. Regulates transcription elongation in a TATA box-dependent manner. Necessary for TAT-dependent activation of the human immunodeficiency virus type 1 (HIV-1) promoter.<ref>PMID:9315662</ref> <ref>PMID:11604498</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/nn/2nnt_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=2nnt ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human CA150, a transcriptional activator, binds to and is co-deposited with huntingtin during Huntington's disease. The second WW domain of CA150 is a three-stranded beta-sheet that folds in vitro in microseconds and forms amyloid fibers under physiological conditions. We found from exhaustive alanine scanning studies that fibrillation of this WW domain begins from its denatured conformations, and we identified a subset of residues critical for fibril formation. We used high-resolution magic-angle-spinning NMR studies on site-specific isotopically labeled fibrils to identify abundant long-range interactions between side chains. The distribution of critical residues identified by the alanine scanning and NMR spectroscopy, along with the electron microscopy data, revealed the protofilament repeat unit: a 26-residue non-native beta-hairpin. The structure we report has similarities to the hairpin formed by the A(beta)((1-40)) protofilament, yet also contains closely packed side-chains in a "steric zipper" arrangement found in the cross-beta spine formed from small peptides from the Sup35 prion protein. Fibrillation of unrelated amyloidogenic sequences shows the common feature of zippered repeat units that act as templates for fiber elongation.
Human CA150, a transcriptional activator, binds to and is co-deposited with huntingtin during Huntington's disease. The second WW domain of CA150 is a three-stranded beta-sheet that folds in vitro in microseconds and forms amyloid fibers under physiological conditions. We found from exhaustive alanine scanning studies that fibrillation of this WW domain begins from its denatured conformations, and we identified a subset of residues critical for fibril formation. We used high-resolution magic-angle-spinning NMR studies on site-specific isotopically labeled fibrils to identify abundant long-range interactions between side chains. The distribution of critical residues identified by the alanine scanning and NMR spectroscopy, along with the electron microscopy data, revealed the protofilament repeat unit: a 26-residue non-native beta-hairpin. The structure we report has similarities to the hairpin formed by the A(beta)((1-40)) protofilament, yet also contains closely packed side-chains in a "steric zipper" arrangement found in the cross-beta spine formed from small peptides from the Sup35 prion protein. Fibrillation of unrelated amyloidogenic sequences shows the common feature of zippered repeat units that act as templates for fiber elongation.


==About this Structure==
General structural motifs of amyloid protofilaments.,Ferguson N, Becker J, Tidow H, Tremmel S, Sharpe TD, Krause G, Flinders J, Petrovich M, Berriman J, Oschkinat H, Fersht AR Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16248-53. Epub 2006 Oct 23. PMID:17060612<ref>PMID:17060612</ref>
2NNT 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=2NNT OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
General structural motifs of amyloid protofilaments., Ferguson N, Becker J, Tidow H, Tremmel S, Sharpe TD, Krause G, Flinders J, Petrovich M, Berriman J, Oschkinat H, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16248-53. Epub 2006 Oct 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17060612 17060612]
</div>
<div class="pdbe-citations 2nnt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Becker, J.]]
[[Category: Becker J]]
[[Category: Berriman, J.]]
[[Category: Berriman J]]
[[Category: Ferguson, N.]]
[[Category: Ferguson N]]
[[Category: Fersht, A R.]]
[[Category: Fersht AR]]
[[Category: Flinders, J.]]
[[Category: Flinders J]]
[[Category: Krause, G.]]
[[Category: Krause G]]
[[Category: Oschkinat, H.]]
[[Category: Oschkinat H]]
[[Category: Petrovich, M.]]
[[Category: Petrovich M]]
[[Category: Sharpe, T D.]]
[[Category: Sharpe TD]]
[[Category: Tidow, H.]]
[[Category: Tidow H]]
[[Category: Tremmel, S.]]
[[Category: Tremmel S]]
[[Category: beta-hairpin]]
[[Category: ca150 second ww domain]]
[[Category: fbp28 protofilament]]
[[Category: fibre]]
 
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