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

Abstract:

: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.

authors

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

doi

10.1006/bbrc.2001.5783

subject

Has Abstract

pub_date

2001-11-02 00:00:00

pages

703-10

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(01)95783-3

journal_volume

288

pub_type

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