Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly.

ABSTRACT: 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 existen

SUBMITTER: Otzen DE 

PROVIDER: S-EPMC27622 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature