Effects of Mutations and Post-Transla- tional Modifications on a-Synuclein In Vitro Aggregation

被引：23

作者：

Pancoe, Samantha X. ^{[1
]}

Wang, Yanxin J. ^{[1
]}

Shimogawa, Marie ^{[1
]}

Perez, Ryann M. ^{[1
]}

Giannakoulias, Sam ^{[1
]}

Otzen, Daniel ^{[1
]}

机构：

[1] Univ Penn, Dept Chem, 231 South 34th St, Philadelphia, PA 19104 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2022年 / 434卷 / 23期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

HUMAN ALPHA-SYNUCLEIN; REVEALS STRUCTURAL DIFFERENCES; N-TERMINAL ACETYLATION; PARKINSONS-DISEASE; LEWY BODY; WILD-TYPE; POSTTRANSLATIONAL MODIFICATIONS; AMYLOID FORMATION; THIOFLAVIN-T; FLUORESCENCE POLARIZATION;

D O I：

10.1016/j.jmb.2022.167859

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibrillar aggregates of the a-synuclein (alpha S) protein are the hallmark of Parkinson's Disease and related neurodegenerative disorders. Characterization of the effects of mutations and post-translational modifica-tions (PTMs) on the aS aggregation rate can provide insight into the mechanism of fibril formation, which remains elusive in spite of intense study. A comprehensive collection (375 examples) of mutant and PTM aggregation rate data measured using the fluorescent probe thioflavin T is presented, as well as a sum-mary of the effects of fluorescent labeling on aS aggregation (20 examples). A curated set of 131 single mutant de novo aggregation experiments are normalized to wild type controls and analyzed in terms of structural data for the monomer and fibrillar forms of alpha S. These tabulated data serve as a resource to the community to help in interpretation of aggregation experiments and to potentially be used as inputs for computational models of aggregation.(c) 2022 Elsevier Ltd. All rights reserved.

引用

页数：35

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