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New page: left|200px<br /> <applet load="1qjh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qjh, resolution 2.20Å" /> '''PROTEIN AGGREGATION... |
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== | ==Protein Aggregation and Alzheimer's Disease: Crystallographic Analysis of the Phenomenon. Engineered version of the ribosomal protein S6 used as a stable scaffold to study oligomerization.== | ||
Limited solubility and precipitation of amyloidogenic sequences such as | <StructureSection load='1qjh' size='340' side='right'caption='[[1qjh]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1qjh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QJH 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1qjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qjh OCA], [https://pdbe.org/1qjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qjh RCSB], [https://www.ebi.ac.uk/pdbsum/1qjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qjh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RS6_THETH RS6_THETH] Located on the outer edge of the platform on the body of the 30S subunit (By similarity). | |||
== 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/qj/1qjh_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=1qjh ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (beta-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a beta-AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest beta-AP homology crystallizes as a tetramer that is linked by the beta-AP residues forming intermolecular antiparallel beta-sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of "structural gatekeepers" in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence. | |||
Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly.,Otzen DE, Kristensen O, Oliveberg M Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9907-12. PMID:10944185<ref>PMID:10944185</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1qjh" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Ribosomal protein S6|Ribosomal protein S6]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
[[Category: Kristensen | [[Category: Kristensen O]] | ||
[[Category: Oliveberg | [[Category: Oliveberg M]] | ||
[[Category: Otzen | [[Category: Otzen DE]] | ||
Latest revision as of 15:46, 13 December 2023
Protein Aggregation and Alzheimer's Disease: Crystallographic Analysis of the Phenomenon. Engineered version of the ribosomal protein S6 used as a stable scaffold to study oligomerization.Protein Aggregation and Alzheimer's Disease: Crystallographic Analysis of the Phenomenon. Engineered version of the ribosomal protein S6 used as a stable scaffold to study oligomerization.
Structural highlights
FunctionRS6_THETH Located on the outer edge of the platform on the body of the 30S subunit (By similarity). 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 PubMedLimited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (beta-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a beta-AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest beta-AP homology crystallizes as a tetramer that is linked by the beta-AP residues forming intermolecular antiparallel beta-sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of "structural gatekeepers" in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence. Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly.,Otzen DE, Kristensen O, Oliveberg M Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9907-12. PMID:10944185[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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