The β‐turn‐supporting motif in the polyglutamine binding peptide QBP1 is essential for inhibiting huntingtin aggregation,FEBS Letters

当前位置： X-MOL 学术 › FEBS Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The β‐turn‐supporting motif in the polyglutamine binding peptide QBP1 is essential for inhibiting huntingtin aggregation
FEBS Letters ( IF 3.0 ) Pub Date : 2020-07-11 , DOI: 10.1002/1873-3468.13873
Vinay Kumar Belwal ₁ , Debika Datta ₁ , Nitin Chaudhary ₁

Affiliation

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.

中文翻译：

聚谷氨酰胺结合肽 QBP1 中的 β-转角支持基序对于抑制亨廷顿蛋白聚集至关重要

聚谷氨酰胺蛋白的聚集是几种神经退行性疾病的标志。11 残基聚谷氨酰胺结合肽 Ac-SNWKWWPGIFD-am，称为 QBP1，可抑制聚谷氨酰胺聚集。此外，文献中报道了 QBP1 肽 (Ac-WKWWPGIF-am) 中的最小 8 个残基延伸以保留该活性。两种肽都含有 Pro-Gly 二肽基序，这是潜在 β 转角区域的特征。在这里，我们研究了这种 β-转角基序的存在是否是抑制亨廷顿蛋白聚集所必需的，亨廷顿蛋白聚集是一种与亨廷顿病有关的聚谷氨酰胺蛋白。使用单个氨基酸取代生成可以支持、引入或消除 β-转角的类似物，我们表明转角支持基序对于 QBP1 介导的亨廷顿蛋白聚集抑制至关重要。

更新日期：2020-07-11

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11