1qjh: Difference between revisions

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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.

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, 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 StructureAbout this Structure

1QJH is a Single protein structure of sequence from Thermus thermophilus with MG as ligand. Structure known Active Site: MG. 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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	[[Category: ribosomal protein s6]]		[[Category: ribosomal protein s6]]

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