Amino acid sequence requirements of peptides that inhibit polyglutamine-protein aggregation and cell death.

Published

Journal Article

Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases including Huntington's disease. In a previous paper, we identified peptides that inhibit polyglutamine protein aggregation and cell death and now describe the amino acid sequence requirements necessary for these activities. The original 11 amino acid polyglutamine (Q) Binding Peptide 1(QBP1; SNWKWWPGIFD) can be shortened to 8 amino acids (WKWWPGIF) without loss of ability to inhibit polyglutamine aggregation. Three determinants are responsible for inhibition: a tryptophan-rich motif (WKWW), a spacer amino acid and the tripeptide GIF. GIF can be replaced by a repeat of the tryptophan-rich motif, but the spacer remains necessary. We also demonstrate concordance between peptide activity in the in vitro assay and a cellular assay of polyglutamine aggregation and cell death. Polyglutamine binding peptides targeted for intracellular delivery by fusion to TAT retain the ability to inhibit polyglutamine aggregation and cell death in transfected COS 7 cells.

Full Text

Duke Authors

Cited Authors

  • Ren, H; Nagai, Y; Tucker, T; Strittmatter, WJ; Burke, JR

Published Date

  • November 2, 2001

Published In

Volume / Issue

  • 288 / 3

Start / End Page

  • 703 - 710

PubMed ID

  • 11676500

Pubmed Central ID

  • 11676500

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.2001.5783

Language

  • eng

Conference Location

  • United States