umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
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.
Identifiers
URN: urn:nbn:se:umu:diva-8763DOI: doi:10.1073/pnas.160086297OAI: oai:DiVA.org:umu-8763DiVA: 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
Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 17 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf