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.
[RS6_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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Otzen DE, Kristensen O, Oliveberg M. Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly. Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9907-12. PMID:10944185 doi:10.1073/pnas.160086297
