1cqm
From Proteopedia
(New page: 200px<br /><applet load="1cqm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cqm, resolution 1.65Å" /> '''PROTEIN AGGREGATION ...) |
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| - | [[Image:1cqm.gif|left|200px]]<br /><applet load="1cqm" size=" | + | [[Image:1cqm.gif|left|200px]]<br /><applet load="1cqm" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1cqm, resolution 1.65Å" /> | caption="1cqm, resolution 1.65Å" /> | ||
'''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.'''<br /> | '''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.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Limited solubility and precipitation of amyloidogenic sequences such as | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1CQM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http:// | + | 1CQM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kristensen, O.]] | [[Category: Kristensen, O.]] | ||
[[Category: Oliveberg, M.]] | [[Category: Oliveberg, M.]] | ||
| - | [[Category: Otzen, D | + | [[Category: Otzen, D E]] |
[[Category: alzheimer disease]] | [[Category: alzheimer disease]] | ||
[[Category: oligomerization]] | [[Category: oligomerization]] | ||
[[Category: ribosomal protein s6]] | [[Category: ribosomal protein s6]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:41 2008'' |
Revision as of 10:08, 21 February 2008
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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.
Overview
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.
About this Structure
1CQM is a Single protein structure of sequence from Thermus thermophilus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 12:08:41 2008
