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The β‐turn‐supporting motif in the polyglutamine binding peptide QBP1 is essential for inhibiting huntingtin aggregation
Author(s) -
Belwal Vinay Kumar,
Datta Debika,
Chaudhary Nitin
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13873
Subject(s) - huntingtin , peptide , huntingtin protein , dipeptide , chemistry , amino acid residue , amino acid , biochemistry , sequence motif , microbiology and biotechnology , peptide sequence , biology , gene , mutant
Aggregation of polyglutamine proteins is a hallmark of several neurodegenerative diseases. The 11‐residue polyglutamine binding peptide Ac‐SNWKWWPGIFD‐am, known as QBP1, inhibits polyglutamine aggregation. Besides, a minimal 8‐residue stretch in the QBP1 peptide (Ac‐WKWWPGIF‐am) is reported in the literature to retain this activity. Both peptides harbor a Pro‐Gly dipeptide motif, a feature characteristic of potential β‐turn regions. Here, we investigated whether the presence of this β‐turn motif is necessary for the inhibition of huntingtin aggregation, a polyglutamine protein implicated in Huntington’s disease. Using single amino acid substitutions to generate analogs that could support, introduce, or eliminate the β‐turn, we show that the turn‐supporting motif is essential for QBP1‐mediated inhibition of huntingtin aggregation.