Characterizing the assembly of the sup35 yeast prion fragment, GNNQQNY : structural changes accompany a fiber-to-crystal switch
Marshall, Karen E., Hicks, Matthew R., Williams, T. L. (Thomas L.), Hoffmann, Soren Vronning, Rodger, Alison, Dafforn, Tim and Serpell, Louise C.. (2010) Characterizing the assembly of the sup35 yeast prion fragment, GNNQQNY : structural changes accompany a fiber-to-crystal switch. Biophysical Journal, Vol.98 (No.2). pp. 330-338. ISSN 0006-3495Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bpj.2009.10.020
Amyloid-like fibrils can be formed by many different proteins and peptides. The structural characteristics of these fibers are very similar to those of amyloid fibrils that are deposited in a number of protein misfolding diseases, including Alzheimer's disease and the transmissible spongiform encephalopathies. The elucidation of two crystal structures from an amyloid-like fibril-forming fragment of the yeast prion, Sup35, with sequence GNNQQNY, has contributed to knowledge regarding side-chain packing of amyloid-forming peptides. Both structures share a cross-beta steric zipper arrangement but vary in the packing of the peptide, particularly in terms of the tyrosine residue. We investigated the fibrillar and crystalline structure and assembly of the GNNQQNY peptide using x-ray fiber diffraction, electron microscopy, intrinsic and quenched tyrosine fluorescence, and linear dichroism. Electron micrographs reveal that at concentrations between 0.5 and 10 mg/mL, fibers form initially, followed by crystals. Fluorescence studies suggest that the environment of the tyrosine residue changes as crystals form. This is corroborated by linear dichroism experiments that indicate a change in the orientation of the tyrosine residue over time, which suggests that a structural rearrangement occurs as the crystals form. Experimental x-ray diffraction patterns from fibers and crystals also suggest that these species are structurally distinct. A comparison of experimental and calculated diffraction patterns contributes to an understanding of the different arrangements accessed by the peptide.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Amyloid, Prions, Yeast, Crystallization, Peptides, Proteins -- Conformation|
|Journal or Publication Title:||Biophysical Journal|
|Official Date:||20 January 2010|
|Number of Pages:||9|
|Page Range:||pp. 330-338|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Alzheimer's Research Trust, Engineering and Physical Sciences Research Council (EPSRC), Lundbeck Foundation, Danish Council for Independent Research. Natural Sciences (FNU)|
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