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DOI | 10.1038/s41467-019-09574-3 |
Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core | |
Lin, Hsiang-Kai1; Boatz, Jennifer C.1; Krabbendam, Inge E.2; Kodali, Ravindra1; Hou, Zhipeng3,4; Wetzel, Ronald1; Dolga, Amalia M.2; Poirier, Michelle A.3; van der Wel, Patrick C. A.1 | |
2019-04-09 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Netherlands |
英文摘要 | Polyglutamine expansion in the huntingtin protein is the primary genetic cause of Huntington's disease (HD). Fragments coinciding with mutant huntingtin exon1 aggregate in vivo and induce HD-like pathology in mouse models. The resulting aggregates can have different structures that affect their biochemical behaviour and cytotoxic activity. Here we report our studies of the structure and functional characteristics of multiple mutant htt exon1 fibrils by complementary techniques, including infrared and solid-state NMR spectroscopies. Magic-angle-spinning NMR reveals that fibrillar exon1 has a partly mobile alpha-helix in its aggregation-accelerating N terminus, and semi-rigid polyproline II helices in the proline-rich flanking domain (PRD). The polyglutamine-proximal portions of these domains are immobilized and clustered, limiting access to aggregation-modulating antibodies. The polymorphic fibrils differ in their flanking domains rather than the polyglutamine amyloid structure. They are effective at seeding polyglutamine aggregation and exhibit cytotoxic effects when applied to neuronal cells. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000401960300001 |
WOS关键词 | NUCLEAR-MAGNETIC-RESONANCE ; ANGLE-SPINNING NMR ; SOLID-STATE ; MUTANT HUNTINGTIN ; ALPHA-SYNUCLEIN ; PROTEIN AGGREGATION ; ROTATING SOLIDS ; TOXICITY ; SPECTROSCOPY ; SEQUENCES |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204311 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Pittsburgh, Sch Med, Dept Biol Struct, 3501 Fifth Ave, Pittsburgh, PA 15213 USA; 2.Univ Groningen, Groningen Res Inst Pharm, Dept Mol Pharmacol, Antonius Deusinglaan 1, NL-9713 AB Groningen, Netherlands; 3.Johns Hopkins Univ, Sch Med, Childrens Med Surg Ctr, Div Neurobiol,Dept Psychiat, 600 N Wolfe St, Baltimore, MD 21287 USA; 4.Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA |
推荐引用方式 GB/T 7714 | Lin, Hsiang-Kai,Boatz, Jennifer C.,Krabbendam, Inge E.,et al. Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Lin, Hsiang-Kai.,Boatz, Jennifer C..,Krabbendam, Inge E..,Kodali, Ravindra.,Hou, Zhipeng.,...&van der Wel, Patrick C. A..(2019).Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core.NATURE COMMUNICATIONS,8. |
MLA | Lin, Hsiang-Kai,et al."Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core".NATURE COMMUNICATIONS 8(2019). |
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