1qjh
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.
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OverviewOverview
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, ... [(full description)]
About this StructureAbout this Structure
1QJH is a [Single protein] structure of sequence from [Thermus thermophilus] with MG as [ligand]. Full crystallographic information is available from [OCA].
ReferenceReference
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
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