Change search
ReferencesLink to record
Permanent link

Direct link
Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: A structural clue to amyloid assembly
Umeå University, Faculty of Science and Technology, Chemistry.
2000 (English)In: PNAS, 9907-12 p.Article in journal (Refereed) Published
Abstract [en]

Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (-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 -AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest -AP homology crystallizes as a tetramer that is linked by the -AP residues forming intermolecular antiparallel -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.

Place, publisher, year, edition, pages
2000. 9907-12 p.
URN: urn:nbn:se:umu:diva-8763DOI: doi:10.1073/pnas.160086297OAI: diva2:148434
Available from: 2008-02-11 Created: 2008-02-11 Last updated: 2011-01-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 14 hits
ReferencesLink to record
Permanent link

Direct link