Solution structure of polyglutamine tracts in GST‐polyglutamine fusion proteins

FEBS Letters

Leonard, Kevin¹  Masino, Laura³  Pastore, Annalisa³  Kelly, Geoff³  Trottier, Yvon² 

[1] EMBL, Meyerhofstrasse 1, D69117 Heidelberg, Germany;IGBMC, CNRS, INSERM, ULP, Université de Strasbourg, Illkirch Cedex 67404, France;National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK

关键词: Aggregation;    Glutathione S-transferase;    Huntington;    Polyglutamine;    Structure;    AU;    analytical ultracentrifugation;    CD;    circular dichroism;    EM;    electron microscopy;    GST;    glutathione S-transferase;    GST-Q22;    fusion protein containing GST and 22 glutamines;    GST-Q41;    fusion protein containing GST and 41 glutamines;    HSQC;    hetero single quantum coherence;    NMR;    nuclear magnetic resonance;    polyQ;    polyglutamine;    Q;    glutamine;    TOCSY;    total correlation spectroscopy;    UV;    ultraviolet;   

DOI  :  10.1016/S0014-5793(02)02335-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Aggregation of expanded polyglutamine (polyQ) seems to be the cause of various genetic neurodegenerative diseases. Relatively little is known as yet about the polyQ structure and the mechanism that induces aggregation. We have characterised the solution structure of polyQ in a proteic context using a model system based on glutathione S-transferase fusion proteins. A wide range of biophysical techniques was applied. For the first time, nuclear magnetic resonance was used to observe directly and selectively the conformation of polyQ in the pathological range. We demonstrate that, in solution, polyQs are in a random coil conformation. However, under destabilising conditions, their aggregation behaviour is determined by the polyQ length.

【 授权许可】

Unknown