NMR study of the formation and dissolution mechanisms of Sup35 amyloid fibrils.

Sup35 淀粉样原纤维的形成和溶解机制的 NMR 研究。

基本信息

批准号：
23770193
负责人：
OHHASHI Yumiko
金额：
$ 2.66万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

项目摘要

Protein aggregates (amyloid) are common pathological feature of most neurodegenerative diseases. In this study, I investigated the molecular mechanism controlling of determination of amyloid structural polymorphism which affects the clinical state of such diseases, using a yeast prion protein, Sup35. From measurements of several NMR methods focusing on the Sup35 structural fluctuation and local conformation, I found two amyloid initiation sites on Sup35 sequence. Thus, it was conceivable that amyloid structural polymorphism arises from the competition of these two sites. Next, I found the relatively compact local conformation in a part of WT Sup35NM. This result exhibited that the one initiation site is included in this compact area, so another site is advantageous in WT amyloid formation. In conclusion, it was suggested that amyloid structural polymorphism is induced by the destruction of local conformation by amino acid substitution.

蛋白质聚集体（淀粉样蛋白）是大多数神经退行性疾病的常见病理特征。 In this study, I investigated the molecular mechanism controlling of determination of amyloid structural polymorphism which affects the clinical state of such diseases, using a yeast prion protein, Sup35. From measurements of several NMR methods focusing on the Sup35 structural fluctuation and local conformation, I found two amyloid initiation sites on Sup35 sequence.因此，可以想象，淀粉样蛋白结构多态性是由这两个地点的竞争引起的。接下来，我在WT Sup35nm的一部分中发现了相对紧凑的局部构象。该结果表明，一个启动位点包含在这个紧凑的区域中，因此另一个位点在WT淀粉样蛋白形成中是有利的。 In conclusion, it was suggested that amyloid structural polymorphism is induced by the destruction of local conformation by amino acid substitution.

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

酵母プリオンSup35を用いたアミロイド構造多形形成メカニズムの解明

使用酵母朊病毒Sup35阐明淀粉样蛋白结构多态性形成的机制

DOI：
发表时间：
2013
期刊：
影响因子：
0
作者：
大橋祐美子;山口芳樹;鎌足雄司;花島慎弥;桑田一夫;田中元雅
通讯作者：
田中元雅

Radically Different Amyloid Conformations Dictate the Seeding Specificity of a Chimeric Sup35 Prion

DOI：
10.1016/j.jmb.2011.02.025
发表时间：
2011-04-22
期刊：
JOURNAL OF MOLECULAR BIOLOGY
影响因子：
5.6
作者：
Foo, Catherine K.;Ohhashi, Yumiko;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.

Structural basis for the diversity of prion strain conformations

朊病毒株构象多样性的结构基础

DOI：
发表时间：
2011
期刊：
影响因子：
0
作者：
Masafumi Shionyu;Ken-ichi Takahashi;Mitiko Go;Yumiko Ohhashi and Motomasa Tanaka
通讯作者：
Yumiko Ohhashi and Motomasa Tanaka

Protein fluctuation in monomer determines prion strain conformations

单体的蛋白质波动决定朊病毒株的构象

DOI：
发表时间：
2012
期刊：
影响因子：
0
作者：
Eisuke Takao;Eri Chatani;Hiroshi Imamura;and Minoru Kato;Yumiko Ohhashi and Motomasa Tanaka
通讯作者：
Yumiko Ohhashi and Motomasa Tanaka

Role of protein fluctuation in determination of amyloid conformation.

蛋白质波动在淀粉样蛋白构象测定中的作用。