Solution structure of polyglutamine tracts in GST-polyglutamine fusion proteins.
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.
Masino
Laura
L
National Institute for Medical Research, The Ridgeway, NW7 1AA, London, UK.
Kelly
Geoff
G
Leonard
Kevin
K
Trottier
Yvon
Y
Pastore
Annalisa
A
D004795:Enzyme Stability; D005982:Glutathione Transferase / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D010455:Peptides; D011993:Recombinant Fusion Proteins; C097188:polyglutamine; D005982:Glutathione Transferase